WO2007115118A1 - Vagus nerve stimulation method - Google Patents
Vagus nerve stimulation method Download PDFInfo
- Publication number
- WO2007115118A1 WO2007115118A1 PCT/US2007/065537 US2007065537W WO2007115118A1 WO 2007115118 A1 WO2007115118 A1 WO 2007115118A1 US 2007065537 W US2007065537 W US 2007065537W WO 2007115118 A1 WO2007115118 A1 WO 2007115118A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- microburst
- microbursts
- series
- pulse
- patient
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36082—Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36128—Control systems
- A61N1/36135—Control systems using physiological parameters
- A61N1/36139—Control systems using physiological parameters with automatic adjustment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
- A61B5/0205—Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/318—Heart-related electrical modalities, e.g. electrocardiography [ECG]
- A61B5/346—Analysis of electrocardiograms
- A61B5/349—Detecting specific parameters of the electrocardiograph cycle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0551—Spinal or peripheral nerve electrodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36053—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for vagal stimulation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36064—Epilepsy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/3611—Respiration control
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
- A61N1/36114—Cardiac control, e.g. by vagal stimulation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36128—Control systems
- A61N1/36146—Control systems specified by the stimulation parameters
- A61N1/36167—Timing, e.g. stimulation onset
- A61N1/36178—Burst or pulse train parameters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/318—Heart-related electrical modalities, e.g. electrocardiography [ECG]
- A61B5/346—Analysis of electrocardiograms
- A61B5/349—Detecting specific parameters of the electrocardiograph cycle
- A61B5/352—Detecting R peaks, e.g. for synchronising diagnostic apparatus; Estimating R-R interval
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/318—Heart-related electrical modalities, e.g. electrocardiography [ECG]
- A61B5/346—Analysis of electrocardiograms
- A61B5/349—Detecting specific parameters of the electrocardiograph cycle
- A61B5/353—Detecting P-waves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/318—Heart-related electrical modalities, e.g. electrocardiography [ECG]
- A61B5/346—Analysis of electrocardiograms
- A61B5/349—Detecting specific parameters of the electrocardiograph cycle
- A61B5/355—Detecting T-waves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/316—Modalities, i.e. specific diagnostic methods
- A61B5/369—Electroencephalography [EEG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/40—Detecting, measuring or recording for evaluating the nervous system
- A61B5/4076—Diagnosing or monitoring particular conditions of the nervous system
- A61B5/4094—Diagnosing or monitoring seizure diseases, e.g. epilepsy
Definitions
- the present invention is directed generally to neurostimulation of the vagus nerve, and more particularly to an improved apparatus and method for vagus nerve stimulation therapy using heart rate variability synchronization, patterned electrical pulses inside a pulse burst, and electroencephalogram ("EEG”) based optimization.
- EEG electroencephalogram
- VNS Vagus nerve stimulation
- VNS TherapyTM for example, VNS TherapyTM by Cyberonics, Inc.
- Vagus nerve stimulation was initially developed and approved by the FDA for the treatment of refractory partial onset epilepsy. Recently, it has been reported that the use of VNS in human patients with epilepsy is associated with an improvement in mood. As a consequence, VNS has also been approved as a treatment for refractory depression (treatment resistant depression).
- VNS typically involves implanting a nerve stimulating electrode on the left or right vagus nerve in the neck.
- the electrode is connected to a subcutaneous pacemaker-like control unit that generates an electrical nerve stimulating signal.
- a Vagus Nerve Stimulator (“VNS stimulator”) is an example of an implantable stopwatch- sized, pace maker- 1 ike control unit device configured to electrically stimulate the vagus nerve leading to the brain.
- VNS is generally applied every 5 minutes in a 7 second to one minute burst (see FIG. 3A for a portion of an exemplary burst) including a pulse train of uniformly spaced apart pulses having a pulse current amplitude of about 0.5 mA to about 2.0 mA).
- the pulses are delivered at about 20 Hz to about 50 Hz.
- Each of the pulses may have a width of about 0.5 milliseconds.
- VNS is currently approved to treat epileptic seizures and depression when drugs have been ineffective. Consequently, a need exists for methods of delivering electrical stimulation to the vagus nerve. Further, a need exists for improved electrical signals that increase the efficacy of VNS.
- the invention includes a method of treating a medical condition by detecting a portion of the QRS wave of the patient's cardiac signal and after detecting the portion of the QRS wave, delivering a microburst comprising 2 to 20 electrical pulses to the patient's vagus nerve.
- a microburst comprising 2 to 20 electrical pulses to the patient's vagus nerve.
- Each of the microbursts may have duration of less than about 100 milliseconds.
- the interpulse intervals separating the pulses are about 3 milliseconds to about 12 milliseconds. In alternate embodiments, the interpulse intervals are less than about 40 milliseconds.
- the sum of the interpulse intervals is less than about 40 milliseconds, and in further embodiments, less than about 60 milliseconds.
- the method includes waiting a predetermined delay period after the detection of the portion of the QRS wave before generating the microburst.
- the invention in another embodiment, includes an exogenous electrical signal delivered to a patient's vagus nerve and adapted to treat a medical condition present in the patient by enhancing the vagal evoked potential in the patient's brain.
- the exogenous electrical signal includes a series of microbursts each having about 2 to about 20 electrical pulses. In some embodiments, the exogenous electrical signal includes a series of microbursts each having a duration less than about one second.
- the invention also includes an implantable device configured to apply the inventive exogenous electrical signal.
- the microbursts of the exogenous electrical signal may be synchronized with the R wave portion of the patient's cardiac cycle.
- each of the microbursts of the exogenous electrical signal occur after a selected R wave portion. In various embodiments, each of the microbursts occurs less than about 1000 milliseconds after the selected R wave portion.
- the pulses of the microbursts may be spaced to simulate the endogenous afferent activity occurring at a particular time in the cardiac cycle. Further, each of the microbursts may be delayed relative to the selected R wave portion to simulate the endogenous afferent activity occurring at a particular time in the cardiac cycle.
- the delay has a duration less than about 500 milliseconds. In further embodiments, the delay has a duration less than about 1000 milliseconds.
- each of the microbursts occurs after an R-R interval (i.e., the amount of time between two successive R wave portions in the cardiac signal) having a duration that is shorter than the duration of the previous R-R interval.
- the microbursts are delivered to the vagus nerve after the R wave portions occurring during inspiration but not after the R wave portions occurring during expiration.
- the invention also includes a method of customizing the exogenous electrical signal to elicit a desired vagal evoked potential in a selected structure of the brain associated with a medical condition.
- the method includes determining a value of a signal parameter (e.g., pulse width, pulse frequency, an interpulse interval between two of the pulses of the microburst, microburst frequency, a number of microbursts of the series of microburst, a duration of the electrical signal, a number of pulses in the microbursts, etc.), generating an electrical signal having a series of microbursts of 2 to 20 electrical pulses each according to the signal parameter, delivering the electrical signal to the patient's vagus nerve, analyzing an EEG of the patient's brain created during the delivery of the electrical signal to determine the vagal evoked potential observed in the selected structure of the brain, and modifying the value of the signal parameter based on the vagal evoked potential observed in the selected structure of the brain to modify the vagal evoke
- Embodiments of the invention also include a computer readable medium having computer executable components for detecting the QRS wave portion of the cardiac cycle, generating a microburst, and delivering the microburst to the vagus nerve of a patient in response to the detection of the QRS wave portion of the patient's cardiac cycle.
- the invention also includes embodiments wherein the patient manually triggers the generation and delivery of the inventive exogenous electrical signal to his/her vagus nerve.
- Figure 1 illustrates a portion of an ECG trace located above a portion of a trace illustrating an exogenous electrical signal patterned into microbursts that are synchronized with the QRS wave portion of the ECG trace.
- Each of the microbursts begins after a delay period following the QRS wave portion of the ECG trace.
- Figure 2A illustrates a conventional electrical signal generator that may be modified to deliver an exogenous electrical signal constructed according to the present invention.
- Figure 2B is a block diagram illustrating various components of the electrical signal generator of Figure 2A.
- Figure 3A is a trace illustrating an exemplary conventional VNS exogenous electrical signal having a series of pulses.
- Figure 3B is a trace of the potential measured in a monkey's thalamus while a portion of the conventional pulse burst of Figure 3A was applied to the vagus nerve of the monkey.
- Figure 3C is a trace illustrating an exemplary embodiment of an exogenous electrical signal constructed according to the present invention.
- Figure 3D is a trace illustrating the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of four pulses each was applied to the vagus nerve.
- the inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds.
- Figure 3E provides nine exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals were applied to the vagus nerve of the monkey.
- Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve.
- Each of the exogenous electrical signals included a series of microbursts having a selected number of pulses each.
- the pulses of the microbursts of the exogenous electrical signals of the topmost row have an interpulse interval of 3 milliseconds.
- the pulses of the microbursts of the exogenous electrical signals of the middle row have an interpulse interval of 6 milliseconds.
- the pulses of the microbursts of the exogenous electrical signals of the bottom row have an interpulse interval of 9 milliseconds.
- Figure 3F provides three exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals were applied to the vagus nerve of the monkey.
- Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve.
- All of the exogenous electrical signals included a series of microbursts having three pulses each. The pulses had an interpulse interval of 9 milliseconds.
- the exogenous electrical signal used to generate the leftmost trace included microbursts separated by an inter-microburst interval of about 6 seconds.
- the exogenous electrical signal used to generate the middle trace included microbursts separated by an inter-microburst interval of about 2 seconds.
- the exogenous electrical signal used to generate the rightmost trace included microbursts separated by an inter-microburst interval of about 0.5 seconds.
- Figure 4A provides four exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals were applied to the vagus nerve of the monkey.
- the inter- microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds.
- a topmost trace illustrates the average potential (after 20 pulses) measured in the monkey thalamus while a pulse burst having a series of uniformly spaced apart pulses was applied to the monkey's vagus nerve. The spacing between the pulses was about 4 seconds.
- a second trace from the top depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each was applied to the vagus nerve.
- a third trace from the top depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of three pulses each was applied to the vagus nerve.
- the bottommost trace depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of four pulses each was applied to the vagus nerve.
- Figure 4B provides five exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals including microbursts having two pulses each, the microbursts being separated by an inter-microburst interval of about 4 seconds, were applied to the vagus nerve of the monkey.
- Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve.
- the interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 40 milliseconds in the topmost trace.
- the interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 20 milliseconds in the trace second from the top.
- the interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 10 milliseconds in the trace third from the top.
- the interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 6.7 milliseconds in the trace fourth from the top.
- the interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 3 milliseconds in the bottommost trace.
- Figure 4C provides five exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals including microbursts having two pulses each, the pulses of each of the microbursts being separated by an interpulse interval of about 6.7 seconds, were applied to the vagus nerve of the monkey.
- Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve.
- the inter-microburst interval between the microbursts of the exogenous electrical signal used in the topmost trace corresponded to the microbursts occurring at a microburst frequency of about 10 Hz.
- the inter-microburst interval between the microbursts of the exogenous electrical signal used in the trace second from the top corresponded to the microbursts occurring at a microburst frequency of about 3 Hz.
- the inter-microburst interval between the microbursts of the exogenous electrical signal used in the trace third from the top corresponded to the microbursts occurring at a microburst frequency of about 1 Hz.
- the inter-microburst interval between the microbursts of the exogenous electrical signal used in the trace fourth from the top corresponded to the microbursts occurring at a microburst frequency of about 0.3 Hz.
- FIG. 5 illustrates a system for using a conventional EEG device to optimize an exogenous electrical signal used for VNS stimulation according to the present disclosure.
- Figure 6 provides an exemplary EEG illustrating the vagal evoked potential elicited by an exogenous electrical signal constructed according to the present invention.
- Figure 7 illustrates an exemplary embodiment of an electrical signal generator programming and/or reprogramming device for use with the electrical signal generator of Figure 2A-2B.
- the present invention provides novel techniques, alone or in combination, to improve the efficacy of VNS used in the treatment of a variety of medical conditions, including disorders of the nervous system, such as epilepsy and depression.
- the following disclosure describes various embodiments of a novel method and its associated apparatus for improving VNS therapies. According to the present disclosure, these novel techniques are particularly useful for treating epilepsy and depression.
- disorders and conditions that include a physiological relationship to the nervous system, such as neuropsychiatric disorders, eating disorders/obesity, traumatic brain injury/coma, addiction disorders, dementia, sleep disorders, pain, migraine, endocrine/pancreatic disorders (including but not limited to diabetes), motility disorders, hypertension, congestive heart failure/cardiac capillary growth, hearing disorders, angina, syncope, vocal cord disorders, thyroid disorders, pulmonary disorders, and reproductive endocrine disorders (including infertility).
- these disorders and conditions including epilepsy and depression, are collectively referred to herein as disorders of the nervous system, even if not conventionally described as such.
- One of the novel techniques includes synchronizing portions of an exogenous electrical signal with the endogenous afferent activity of the vagus nerve, primarily the endogenous afferent activity originating from receptors in the heart and lungs. Stimulating the vagus nerve in synchrony with endogenous vagal rhythms, in particular with cardiac cycle and heart rate variability (HRV), enhances therapeutic efficacy of VNS.
- the exogenous electrical signal applied to the vagus nerve during conventional VNS is often referred to as a pulse burst.
- the pulse burst typically includes a series of uniformly spaced apart substantially identical pulses, i.e., a simple pulse train.
- the VNS applied to treat disorders of the nervous system may include multiple pulse bursts separated by an interburst delay.
- An individual pulse burst may be triggered automatically or manually.
- a pulse burst may be triggered by the detection of a medical event such as a seizure, or may be triggered manually by the user or a medical professional.
- pulse bursts may occur at regular intervals separated by a predetermined interburst delay.
- the interburst delay is about five minutes, 30 minutes, or 60 minutes.
- the pulses of the conventional VNS pulse bursts are applied asynchronously, i.e., asynchronous with both the cardiac and lung cycles.
- conventional VNS is generally applied every 5 minutes in a 7 second to one minute pulse burst (see FIG. 3A for a portion of an exemplary burst) of uniformly spaced apart pulses having an pulse current amplitude of about 0.5 mA to about 2.0 mA.
- the pulses are delivered at about 20 Hz to about 50 Hz.
- Each of the pulses may have a width of about 0.5 milliseconds. While monophasic pulses are generally used, biphasic pulses may also be used.
- the term "pulses" refers to both monophasic and biphasic pulses.
- the pulses within a pulse burst are patterned or otherwise organized to improve and/or optimize stimulation of the vagus nerve and/or structures of the brain in communication therewith.
- the natural endogenous afferent activity in the left and right vagus nerves predominantly occurs immediately following each cardiac contraction and during each inspiration. Further, the timing of the endogenous afferent activity in the left and right vagus nerves varies with heart rate, breathing rate, and emotional state.
- vagus nerve may refer to either the left or right vagus nerve.
- a novel exogenous electrical signal is applied to the vagus nerve.
- the novel exogenous electrical signal is configured to augment the natural endogenous afferent activity in the vagus nerve by timing the pulses within a pulse burst in an improved and more effective manner.
- the pulses within the pulse burst may be organized into sub-bursts or microbursts (each having about 2 to about 20 pulses) that are synchronized with the endogenous afferent activity in the vagus nerve to augment the endogenous afferent activity therein.
- a trace 100 of a portion of an exemplary embodiment of the novel exogenous electrical signal is provided.
- an exemplary electrocardiogram (ECG) trace 120 depicting cardiac activity detected by an electrocardiograph (not shown) is provided.
- the novel exogenous electrical signal includes a pulse burst 130 organized into a series of microbursts 170. Each of the microbursts 170 is synchronized with a portion of the cardiac cycle depicted in the ECG trace 120.
- each of the microbursts 170 is synchronized with the QRS wave portion 174 of the ECG trace 120, so that endogenous cardiac-related and respiration-related vagal afferent activity is augmented by the microbursts 170 of the exogenous electrical signal.
- each of the microbursts 170 may be triggered by an R-wave portion 176 of the QRS wave portion 174.
- synchronizing the application of the microbursts 170 of the exogenous electrical signal to the vagus nerve with the detection of the R-wave portion 176 of the patient's cardiac cycle may increase the efficacy of VNS therapy by entraining the exogenous electrical signal with the endogenous cyclic facilitation of central vagal afferent pathways.
- Each of the microbursts 170 begins after the elapse of a delay period, which comprises a variable time period that may range, e.g., from about 10 milliseconds to about 1000 milliseconds following detection of the R-wave portion 176.
- the delay period may be less than about 10 milliseconds.
- the delay period may be about 10 milliseconds to about 500 milliseconds or about 10 milliseconds to about 800 milliseconds.
- the delay period is less than 1000 milliseconds. In other embodiments, the delay period may be omitted.
- Each of the delay periods may comprise a predetermined duration such as about 10 milliseconds, or may comprise a random time duration within a predetermined minimum and maximum time duration, e.g., a random time duration from about 10 milliseconds to about 1000 milliseconds. Further, as will be described below, the duration of the delay period preceding each microburst 170 may be determined empirically.
- the leftmost (first) microburst 170 begins after a delay period "D1 ,” the next (or second) microburst 170 begins after a delay period “D2,” and the third microburst 170 begins after a delay period “D3.”
- the delay period “D1” may be shorter than the delay periods “D2” and “D3.”
- the delay period “D2” may be shorter than the delay period “D3.”
- the delay periods “D1 ,” “D2,” and “D3" may be substantially identical.
- the delay period "D1 ,” may be larger than delay period “D2,” which may be larger than delay period “D3.”
- Embodiments wherein each of the delay periods “D1 ,” “D2,” and “D3" is selected randomly within a specified range of delay values or determined empirically are also within the scope of the present invention.
- still further embodiments of the present invention may include a variety of delay period combinations that can be identified and implemented by routine experimentation. Each of these is considered to be within the scope of the present invention. While three delay periods have been described with respect to Fig. 1 , it is apparent to those of ordinary skill that a delay period may precede each microburst of a pulse burst and the duration of the delay period may be determined empirically or randomly.
- the synchronization of the exogenous electrical signal further comprises not providing pulses during selected portions of the cardiac cycle, such as periods in the opposite half of the cardiac and respiratory duty cycles, when the central pathways are inhibited.
- pulses applied to the vagus nerve during the opposite half of the cardiac and respiratory duty cycles are less effective because endogenous signals in this part of the cardiac and/or respiratory cycles are less significant, in terms of their information content, for modulating those portions of the brain relevant to homeostasis mechanisms implicated in medical conditions such as epilepsy and depression.
- at least a portion of the asynchronous exogenous electrical signal delivered by current stimulation algorithms, such as conventional VNS may be therapeutically irrelevant.
- the exogenous electrical signal is typically delivered by an implanted device powered by a battery, the delivery of irrelevant signals may result in unnecessary battery depletion. Further, the pulse burst sometimes causes the patient's vocal cords to contract causing his/her voice to become horse, which is uncomfortable and makes talking difficult. Sometimes, the pulse burst causes neck pain and may cause cardiac problems. Therefore, reducing the number of pulses may contribute to patient comfort and/or safety. Synchronizing the microbursts 170 of the exogenous electrical signal with each individual QRS wave portion 174 also tracks the natural variability in vagal afferent activity that occurs during breathing and emotional shifts. This heart rate variability (HRV) is a function of respiration and efferent sympathovagal tone.
- HRV heart rate variability
- HRV is also known as respiratory sinus arrhythmia. Additionally, it is well established that a larger HRV is associated with greater physical health, including greater immune function, lower risk of cardiac arrhythmia, and better mood, than a smaller HRV.
- HRV is greatly increased during meditation, and HRV is increased easily by slow, paced breathing.
- Synchronizing the microbursts 170 of the exogenous electrical signal with each QRS wave portion 174 of the cardiac cycle utilizes and accentuates the positive association of HRV with overall bodily health. Further, it helps ensure that the microbursts 170 of the exogenous electrical signal are synchronized with variances in the cardiac cycle. Consequently, it may be beneficial for the patient to begin paced breathing during the pulse burst. Further, it may improve the efficacy of the exogenous electrical signal if the pulse burst is triggered while the patient is performing paced breathing. Referring to FIG.
- a suitable electrical signal generator 200 such as a VNS stimulator, known in the art has one or more electrodes 220A and 220B coupled to the vagus nerve for delivering electrical pulses thereto.
- the electrical signal generator 200 has the capacity to detect cardiac signals and produce an ECG trace for the purpose of avoiding the deliverance of conventional VNS in the event of cardiac arrest.
- the suitable electrical signal generator 200 for use with the present invention may include one or more sensors, such as sensing electrodes 210A and 210B positioned to detect cardiac electrical signals, and the onboard capability of analyzing those signals.
- the electrical signal generator 200 may be capable of identifying the R wave portion of the cardiac signal.
- the sensor(s) may include an acoustic device configured to detect the cardiac cycle.
- the electrical signal generator 200 may be modified or programmed to deliver the novel exogenous electrical signal.
- the modifications include replacing a more common open-loop or non-feedback stimulation system with a feedback system utilizing one or more sensing electrodes 210A and 21 OB to detect the QRS wave portion 174 of the ECG trace 120 (see FIG. 1 ).
- the modification of the electrical signal generator 200 is effected by programming the electrical signal generator 200 to initiate a microburst 170 after the elapse of the delay period, such as delay period "D1 ", delay period "D2", or delay period "D3,” following the detection of the QRS wave portion 174.
- a delay period may precede each microburst and such embodiments are within the scope of the present invention. Further, embodiments in which no delay period precedes a microburst are also within scope of the present invention. As is apparent to those of ordinary skill in the art, embodiments of the electrical signal generator 200 that have the feedback system for detecting the QRS wave portion 174 without modification are also within the scope of the present invention.
- FIG. 2B is a block diagram of various components of the electrical signal generator 200.
- the electrical signal generator 200 may include a programmable central processing unit (CPU) 230 which may be implemented by any known technology, such as a microprocessor, microcontroller, application-specific integrated circuit (ASIC), digital signal processor (DSP), or the like.
- the CPU 230 may be integrated into an electrical circuit, such as a conventional circuit board, that supplies power to the CPU 230.
- the CPU 230 may include internal memory or memory 240 may be coupled thereto.
- the memory 240 is a computer readable medium that includes instructions or computer executable components that are executed by the CPU 230.
- the memory 240 may be coupled to the CPU 230 by an internal bus 250.
- the memory 240 may comprise random access memory (RAM) and readonly memory (ROM).
- the memory 240 contains instructions and data that control the operation of the CPU 230.
- the memory 240 may also include a basic input/output system (BIOS), which contains the basic routines that help transfer information between elements within the electrical signal generator 200.
- BIOS basic input/output system
- the present invention is not limited by the specific hardware component(s) used to implement the CPU 230 or memory 240 components of the electrical signal generator 200.
- the electrical signal generator 200 may also include an external device interface 260 permitting the user or a medical professional to enter control commands, such as a command triggering the delivery of the novel exogenous electrical signal, commands providing new instructions to be executed by the CPU 230, commands changing parameters related to the novel exogenous electrical signal delivered by the electrical signal generator 200, and the like, into the electrical signal generator 200.
- the external device interface 260 may include a wireless user input device.
- the external device interface 260 may include an antenna (not shown) for receiving a command signal, such as a radio frequency (RF) signal, from a wireless user input device such as a computer-controlled programming wand 800 (see FIG. 7).
- the electrical signal generator 200 may also include software components for interpreting the command signal and executing control commands included in the command signal. These software components may be stored in the memory 240.
- the electrical signal generator 200 includes a cardiac signal interface 212 coupled to sensing electrodes 210A and 210B for receiving cardiac electrical signals.
- the cardiac signal interface 212 may include any standard electrical interface known in the art for connecting a signal carrying wire to a conventional circuit board as well as any components capable of communicating a low voltage time varying signal received from the sensing electrodes 21 OA and 21 OB through an internal bus 214 to the CPU 230.
- the cardiac signal interface 212 may include hardware components such as memory as well as standard signal processing components such as an analog to digital converter, amplifiers, filters, and the like.
- the electrical signal generator 200 includes an exogenous electrical signal interface 222 coupled to electrodes 220A and 220B for delivering the exogenous electrical signal to the vagus nerve.
- the exogenous electrical signal interface 222 may include any standard electrical interface known in the art for connecting a signal carrying wire to a conventional circuit board as well as any components capable of communicating a low voltage time varying signal generated by the CPU 230 or a signal generating device controlled by the CPU 230 to the electrodes 220A and 220B through an internal bus 252.
- the exogenous electrical signal interface 222 may include hardware components such as memory as well as standard signal processing components such as a digital to analog converter, amplifiers, filters, and the like.
- the various components of the electrical signal generator 200 may be coupled together by the internal buses 214, 250, 252, and 254.
- Each of the internal buses 214, 250, 252, and 254 may be constructed using a data bus, control bus, power bus, I/O bus, and the like.
- the electrical signal generator 200 may include instructions 280 executable by the CPU 230 for processing and/or analyzing the cardiac electrical signals received by the sensing electrodes 210A and 210B. Additionally, the electrical signal generator 200 may include instructions 280 executable by the CPU 230 for generating an exogenous electrical signal delivered to the vagus nerve by the electrodes 220A and 220B. These instructions may include computer readable software components or modules stored in the memory 240. The instructions 280 may include a Cardiac Signal Monitoring Module 282 that generates a traditional ECG trace from the cardiac electrical signals. The Cardiac Signal Monitoring Module 282 may record the ECG trace in the memory 240.
- generating an ECG trace from an analog cardiac electrical signal may require digital or analog hardware components, such as an analog to digital converter, amplifiers, filters, and the like and such embodiments are within the scope of the present invention.
- some or all of these components may be included in the cardiac signal interface 212.
- some or all of these components may be implemented by software instructions included in the Cardiac Signal Monitoring Module 282.
- the Cardiac Signal Monitoring Module 282 may include any method known in the art for generating an ECG trace from a time varying voltage signal.
- the unmodified electrical signal generator 200 monitors cardiac electrical signals for the purposes of detecting a cardiac arrest.
- the Cardiac Signal Monitoring Module 282 may be modified to include instructions for detecting or identifying the R wave portion of the ECG trace.
- the R wave portion of the ECG trace may be detected using any method known in the art. While the electrical signal generator 200 has been described as having the Cardiac Signal Monitoring Module 282, embodiments in which the functionality of the Cardiac Signal Monitoring Module 282 is performed by more than one software component are within the scope of the present invention.
- the unmodified electrical signal generator 200 generates the exogenous electrical signal used by conventional VNS.
- the instructions 280 include a Signal Generation Module 284 for instructing the CPU 230 how and when to generate the conventional VNS exogenous electrical signal and deliver it to the vagus nerve via the electrodes 220A and 220B.
- the Signal Generation Module 284 may be modified to generate the inventive novel exogenous electrical signal. Specifically, the Signal Generation Module 284 may be modified to include instructions directing the CPU 230 to synchronize the microbursts of the exogenous electrical signal with the R wave portion of the ECG trace.
- the Signal Generation Module 284 may determine the values of the various parameters used to define the novel exogenous electrical signal based on simulating the endogenous afferent activity of the vagus nerve as described herein. Alternatively, the values of the various parameters may be stored in the memory 240 and used by the Signal Generation Module 284 to generate the novel exogenous electrical signal. The various parameters may be entered into the memory 240 by the external device interface 260 which permits the user or medical professional to enter control commands, including commands changing parameters related to the novel exogenous electrical signal delivered by the electrical signal generator 200, and the like, into the electrical signal generator 200.
- While the electrical signal generator 200 has been described as having the Signal Generation Module 284, embodiments in which the functionality of the Signal Generation Module 284 is performed by more than one software component are within the scope of the present invention.
- suitable electrical signal generators for use with the present invention include a model 103 VNS stimulator (formally referred to as the Gen39) produced by Cyberonics, Inc. (Houston, TX), model 104 VNS stimulator also produced by Cyberonics, Inc., and the like.
- the analog recording and ECG recognition capacity of these VNS stimulators enable their onboard processor to be programmed to produce pulse bursts of vagal stimulation having the desired parameters at variable delay periods following the detection of the R-wave of the ECG.
- the delay periods may comprise a predetermined, programmable duration such as about 10 milliseconds, or may comprise a random time duration within a predetermined programmable minimum and maximum time duration, e.g., a random time duration from about 10 milliseconds to about 1000 milliseconds.
- the predetermined, programmable duration(s) of the delay period(s) may be determined empirically using methods described below.
- the electrical signal generator 200 may provide an asynchronous exogenous electrical signal having microbursts spaced at regular or variable intervals.
- the microbursts may occur at least every 100 milliseconds or at the microburst frequency of about 0.25 Hz to about 10 Hz.
- the pulses within the microbursts may be spaced at regular or variable intervals.
- less sophisticated embodiments of the electrical signal generator 200 include electrical signal generators that are pre-programmed with the exogenous electrical signal parameters (e.g., pulse width, pulse frequency, interpulse interval(s), microburst frequency, number of pulses in the microbursts, etc.) before implementation and may retain those pre-programmed parameter values throughout the functional life of the electrical signal generator.
- electrical signal generators configured to generate an asynchronous exogenous electrical signal may be programmable after implementation.
- the computer-controlled programming wand 800 (see FIG. 7) may be used in the manner described above to program such electrical signal generators.
- the present invention is not limited by the particular electrical signal generator used to generate the inventive exogenous electrical signal.
- the microbursts of the exogenous electrical signal may be delivered following every detected R-wave occurring within a predetermined pulse burst period, i.e., the period of time during which the exogenous electrical signal is generated.
- the microbursts may be applied to the vagus nerve only during the inspiratory phase. This may be implemented by programming the electrical signal generator 200 to apply a microburst only on the shortening R-R intervals during HRV, i.e., only on an R-wave having an R-R interval less than the preceding R-R interval, or less than a moving average for several R-R intervals, e.g., less than a 5 or 10 R-R interval moving average.
- the electrical signal generator 200 may include a sensor, such as a strain gauge or acoustic device, that detects various biometric parameters such as heartbeat and the respiratory cycle.
- a strain gauge may be used to determine inspiration is occurring by identifying when the chest is expanding. The invention is not limited by the method used to determine inspiration is occurring, the R-R interval, and/or whether the R-R intervals are shortening for the purposes of determining inspiration is occurring.
- the timing parameters defining how the microbursts of the exogenous electrical signal are synchronized with the cardiac cycle for maximal therapeutic efficacy may be determined empirically, and according to particular embodiments, are individually optimized for each patient (as described below).
- patients may perform paced breathing, e.g., taking a breath at a frequency of about 0.1 Hz, during periods when the exogenous electrical signal is being delivered to the vagus nerve, to facilitate or increase the amount of HRV.
- the various parameters of the cardiac cycle synchronized exogenous electrical signal may be varied, including without limitation the duration of the pulse burst, the delay period(s) following R-wave detection, the number of pulses comprising a microburst, the interpulse interval (i.e., the amount of time separating one pulse from an adjacent pulse), and the inter-microburst interval (i.e., the amount of time between successive microbursts). Further, these parameters may be selectively associated with particular R-waves of the respiratory cycle, depending on the length of each preceding R-R-interval. In various embodiments, these parameters are empirically optimized for each patient.
- a method of providing an exogenous electrical signal capable of inducing a much larger vagal evoked potential (VEP) than that induced by conventional VNS is provided.
- the exogenous electrical signal provided to the vagus nerve comprises a pulse burst including a series of microbursts. As described above the inter-microburst interval may be determined by the cardiac cycle.
- the pulse burst 300 includes a plurality of uniformly spaced apart pulses 302 occurring about every 20 milliseconds to about every 50 milliseconds, i.e., occurring at a frequency of about 20 Hz to about 50 Hz.
- a conventional pulse burst, such as pulse burst 300 may have a pulse burst duration of about 7 seconds to about 60 seconds (resulting in a pulse burst having from about 140 to about 3000 pulses or more).
- Each pulse 302 may have a width or duration of about 50 microseconds to about 1000 microseconds ( ⁇ sec) and a pulse current of about 0.1 mA to about 8 mA.
- the pulse burst 300 may be separated from a pulse burst identical to pulse burst 300 by an interburst interval of about 5 min. Sometimes, an interburst interval of about 30 min. or about 60 min. is used. In further implementations, the pulse burst 300 is triggered by the onset of a medical event, such as a seizure, or is triggered by the user or a medical professional. In such embodiments, the interburst interval varies.
- FIG. 3B provides a trace 304 of the potential measured in the monkey thalamus while the conventional pulse burst 300 (see FIG. 3A) of uniformly spaced pulses 302 having an interpulse interval of 4 seconds was applied to the vagus nerve.
- the trace 304 shows the potential inside the thalamus immediately after each of the pulses 302 is delivered to the vagus nerve.
- An increased VEP 305 occurs after the first pulse 302.
- FIG. 3B little to no increased VEP is observed after the successive pulses 302 in the series.
- the average potential inside the thalamus observed over 20 pulses is provided by a topmost trace 320 in FIG. 4A.
- the VEP is the difference between a minimum average potential in the trace 320 observed after an averaged pulse portion 303 of the trace 320 and a maximum average potential in the trace 320 observed after the averaged pulse portion 303 of the trace 320.
- the minimum and the maximum potentials are not clearly identifiable.
- a portion of a pulse burst 400 of the exogenous electrical signal constructed in accordance with the present invention is provided.
- the pulses 402 and 404 of the pulse burst 400 are patterned or structured within the pulse burst 400. Specifically, the pulses 402 and 404 are arranged into microbursts 41 OA, 41 OB, and 41 OC. In the embodiment depicted in FIG. 3C, each of the microbursts 41 OA, 41 OB, and 41 OC includes the pulse 402 followed by the pulse 404.
- Each of the individual pulses 402 and 404 in the pulse burst 400 resemble the pulses 302 of the conventional VNS pulse burst 300 and have a pulse width of about 50 microseconds to about 1000 microseconds ( ⁇ sec) and a pulse current of about 0.25 mA to about 8 mA. In particular embodiments, the pulse current is less than about 2 mA.
- the conventional pulse burst 300 may have a pulse burst duration of about 7 seconds to about 60 seconds and a pulse frequency of about 20 Hz to about 50 Hz, resulting in a pulse burst having from about 140 to about 3000 pulses or more. If the pulse burst 400 has a duration of about 7 seconds to about 60 seconds, and the microbursts are delivered every 0.5 seconds, roughly corresponding to the interval between heart beats during inspiration, the pulse burst 400 will have about 30 pulses to about 242 pulses.
- reducing the number of pulses delivered to the vagus nerve may help prolong battery life as well as improve patient comfort and safety.
- patterning the pulses of the pulse burst 400 into microbursts, such as microbursts 41 OA, 41 OB, and 41 OC increases the VEP observed in the brain. Because the VEP is increased, the current amplitude may be reduced, further increasing patient comfort and/or safety. The increased VEP may also improve the therapeutic effects of the exogenous electrical signal.
- the microbursts of FIG. 3D are separated by a 4 second inter-microburst interval.
- the VEP is the difference between a minimum 307 in the trace 306 observed after an averaged microburst portion 309 of the trace 306 and a maximum 308 in the trace 306 observed after the averaged microburst portion 309 of the trace 306.
- the difference between the minimum 307 and the maximum 308 of the trace 306 is clearly larger than the difference between the unidentifiable minimum and the unidentifiable maximum of the trace 320 (see FIG. 4A and the pulse intervals after the third pulse in FIG. 3B). Therefore, without changing any parameters other than the number of pulses delivered every 4 sec, i.e., delivering a microburst instead of a single pulse, the VEP potential can be increased or enhanced.
- the pulses 402 and 404 within the first microburst 410A are separated by an interpulse interval "P1 A.”
- the pulses 402 and 404 within the second microburst 41 OB are separated by an interpulse interval "P1 B.”
- the pulses 402 and 404 within the third microburst 41 OC are separated by an interpulse interval "P1 C.”
- the interpulse intervals "P1 A,” “P1 B,”and “P1 C” separating the pulses 402 and 404 are shorter than the interpulse intervals between the pulses 302 used in conventional VNS therapy.
- the first interpulse interval "P1 A” may range from about one millisecond to about 50 milliseconds.
- the first interpulse interval “P1 A” may range from about 2 milliseconds to about 10 milliseconds. In some embodiments, Typically, the first interpulse interval “P1 A” may range from about 3 milliseconds to about 10 milliseconds.
- the interpulse interval "P1 B” may be substantially equal to the interpulse interval "P1 A.” Subsequent interpulse intervals occurring after the interpulse interval “P1 B,” such as interpulse interval “P1 C,” may be substantially equal to the interpulse interval "P1 B.” In alternate embodiments, the interpulse interval “P1 A” may be larger than the interpulse interval “P1 B,” which may be larger than the interpulse interval "P1 C.” In further embodiments, the interpulse interval “P1 A” may be smaller than the interpulse interval "P1 B,” which may be smaller than the interpulse interval "P1 C.” In various embodiments, the interpulse intervals "P1 A,” “P1 B,” and “P1 C” may be selected randomly from a predetermined range of interpulse interval values.
- the interpulse intervals may be variable and determined empirically, as described below.
- the first microburst 41 OA is separated from the microburst 41 OB by an inter-microburst interval "P2."
- Each microburst may be considered an event occurring at a microburst frequency (i.e., the inverse of the sum of the inter-microburst interval "P2" and the duration of the microburst).
- the microburst frequency may range from about 0.25 Hz to about 10 Hz. It may be beneficial to use a microburst frequency that approximates the R-R cycle of the patient.
- the pulses within a microburst may be patterned or structured.
- the pulse burst 130 includes five microbursts 170, each triggered by the R- wave portion 176 of the cardiac cycle depicted in the ECG trace 120.
- Each microburst 170 includes four pulses 182, 184, 186, and 188.
- the first pulse 182 begins after the predetermined delay time "D1 " has elapsed following the identification of the R-wave portion 176.
- the pulse 184 follows the pulse 182 after a first interpulse delay has elapsed. Then, after a second interpulse interval, the pulse 186 is generated.
- the pulse 188 is generated.
- the interpulse intervals increase in duration along the series of pulses.
- the interpulse intervals may be determined empirically and individualized for each patient. While each microburst 170 in FIG. 1 has only four pulses, microbursts 170 having 2 to 20 pulses, and consequently 1 to 19 interpulse intervals, are within the scope of the present invention. In some embodiments, the microbursts 170 may have 2 to 15 pulse, or alternatively, 3 to 6 pulses.
- the pulse burst 400 may be separated from a pulse burst identical to pulse burst 400 or a dissimilar pulse burst by an interburst interval of about 5 minutes to about 240 minutes. Alternatively, the interburst interval may be about 200 milliseconds to about 24 hours. In further embodiments, the pulse burst is applied continuously. The pulse burst may have a duration of about 100 milliseconds to about 60 minutes. In various embodiments, the pulse burst duration is determined empirically for a particular patient and/or medical condition. In further embodiments, the pulse burst 400 is triggered by the onset of a medical event, such as a seizure, or is triggered by the user or a medical professional.
- a medical event such as a seizure
- the interburst interval varies.
- the pulse burst 400 may be terminated automatically by the onset of a medical event, such as cardiac arrest, or manually the user or a medical professional.
- the pulse burst duration varies.
- Pulses, such as pulses 182, 184, 186, and 188, arranged into microbursts, such as microburst 170, are capable of evoking an enhanced vagal evoked potential (eVEP) in the patient's brain that is significantly greater than an VEP evoked by conventional VNS (see FIG. 3A).
- eVEP enhanced vagal evoked potential
- this eVEP may attenuate as the number of pulses within a microburst increases beyond an optimal number of pulses.
- the eVEP attenuates as the microburst duration increases beyond an optimal duration.
- the eVEP begins to diminish, and if more than 20 pulses are provided, the eVEP essentially disappears.
- FIG. 3E Referring to the top row of FIG. 3E, traces 370, 372, and 374 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of 3 milliseconds.
- the microbursts of FIG. 3E are separated by a 4 second inter-microburst interval.
- the number of pulses within the microbursts increase from left to right.
- the microbursts had 2 pulses each.
- the microbursts had 5 pulses each.
- the microbursts had 9 pulses each.
- the VEP observed in each trace is the difference between a minimum in the trace observed after an averaged microburst portion (appearing at the left of the trace) and a maximum in the trace observed after the averaged microburst portion of the trace.
- the top row clearly illustrates that using these parameters, microbursts having 5 pulses produce a larger VEP than microbursts having 2 pulses. However, microbursts having 9 pulses produce a smaller VEP than microbursts having 5 pulses.
- traces 380, 382, and 384 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of 6 milliseconds.
- the microbursts had 2 pulses each.
- the microbursts had 3 pulses each.
- the microbursts had 6 pulses each.
- the middle row clearly illustrates that using these parameters, microbursts having 3 pulses produce a larger VEP than microbursts having 2 pulses. However, microbursts having 6 pulses produce a smaller VEP than microbursts having 3 pulses.
- traces 390, 392, and 394 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of 9 milliseconds.
- the microbursts had 2 pulses each.
- the microbursts had 3 pulses each.
- the microbursts had 5 pulses each.
- the bottom row clearly illustrates that using these parameters, microbursts having 3 pulses produce a larger VEP than microbursts having 2 pulses. However, microbursts having 5 pulses produce a smaller VEP than microbursts having 3 pulses.
- traces 370, 380, and 390 illustrate the facilitation the first pulse provides to the second pulse of the microburst.
- the traces 372, 382, and 392 in the rightmost column of FIG. 3E illustrate additional facilitation provided by adding additional pulses to the microburst.
- the traces 374, 384, and 394 in the rightmost column of FIG. 3E illustrate that if the duration of the microbursts is too long, the microburst extends into an inhibitory period of neural activity reducing the VEP observed in the thalamus of the monkey. Consequently, the VEP may be improved and/or optimized by the selection of the number of pulses of the microbursts.
- FIG. 3E illustrates that the VEP begins to decline when the sum of the interpulse intervals within a single microburst exceeds about 30 milliseconds. Consequently, for the monkey, the optimal sum of the interpulse intervals within a single microburst may be less than 30 milliseconds and in some embodiments, less than 20 milliseconds.
- the data of FIG. 3E further indicates, a range of about 12 milliseconds to about 18 milliseconds may be used.
- the optimal sum of the interpulse intervals within a single microburst may be less than 80 milliseconds and in some embodiments, the sum may be less than 60 milliseconds. In further embodiments, the sum of the interpulse intervals within a single microburst may be less than about 40 milliseconds and preferably about 12 milliseconds to about 40 milliseconds.
- the sum of the interpulse intervals within a single microburst may be about 10 milliseconds to about 80 milliseconds.
- One of ordinary skill in the art will also recognize alternate methods of converting the sum of the interpulse intervals determined in the experimental monkey data for use with a human and that such embodiments are within the scope of the present invention. Further, the sum of the interpulse intervals for use with a human may be determined empirically using the empirical method described below.
- the microburst duration (i.e., the sum of the interpulse intervals and the pulse widths within a microburst) may be less than about one second. In particular embodiments, the microburst duration may be less than about 100 milliseconds. In particular embodiments, microbursts having a duration of about 4 milliseconds to about 40 milliseconds may be used.
- traces 391 , 393, and 395 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of about 9 milliseconds.
- the microbursts used to create the traces 391 , 393, and 395 are separated by about a 6 second, about a 2 second, and about a 0.5 second inter- microburst interval, respectively.
- the trace 395 illustrates that the eVEP is present at the rate the QRS wave occurs in the cardiac cycle during inspiration, i.e., about once every 0.5 second. Consequently, microbursts synchronized with the QRS wave during inspiration may produce eVEP in the thalamus and other brain structures in electrical communication therewith.
- Other parameters such as interpulse interval(s), delay period(s), pulse current amplitude, pulse width, pulse burst duration, and the like may be adjusted to improve and/or optimize the VEP.
- the present invention provides a microburst having only a small number of pulses as well as an inter-microburst interval that serves as a period during which the vagus nerve (and/or brain structures in communication therewith) may recover from the microburst.
- Providing an appropriate inter-microburst interval helps ensure that the succeeding microburst in the pulse burst of the exogenous electrical signal is capable of generating the eVEP.
- the inter-microburst interval is as long as or longer than the duration of the microburst.
- the inter-microburst interval is at least 100 milliseconds.
- the inter-microburst interval may be as long as 4 seconds or 6 seconds.
- the inter-microburst interval may be as long as 10 seconds.
- Each microburst comprises a series of pulses that, in some embodiments, are intended to mimic the endogenous afferent activity on the vagus nerve.
- the microburst may simulate the endogenous afferent vagal action, such as the action potentials associated with each cardiac and respiratory cycle.
- the central vagal afferent pathways involve two or more synapses before producing activity in the forebrain.
- Each synaptic transfer is a potential site of facilitation and a nonlinear temporal filter, for which the sequence of inter-microburst intervals and/or interpulse intervals within a microburst can be optimized. Without being bound by theory, it is believed that the use of microbursts enhances VNS efficacy by augmenting synaptic facilitation and "tuning" the input stimulus train to maximize the forebrain evoked potential.
- FIG. 4A-4C illustrate the effects of modifying the various parameters of the exogenous electrical signal on the VEP measured in the thalamus of a monkey.
- FIG. 4A illustrates the effects of varying the number of pulses in a microburst.
- FIG. 4B illustrates the effects of varying the interpulse interval between the pulses of a microburst having only two pulses.
- FIG. 4C illustrates the effects of varying the inter- microburst interval between adjacent microbursts having only two pulses each.
- the topmost trace 320 of FIG. 4A provides the average potential (after 20 pulses) measured in the monkey thalamus while a pulse burst of uniformly spaced apart pulses having an interpulse interval of 4 seconds was applied to the vagus nerve.
- a trace 340 of FIG. 4A depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each was applied to the vagus nerve.
- the inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds.
- the VEP i.e., the difference between the minimum and maximum potentials observed after each microburst is noticeably improved in the trace 340 when compared with the VEP of the trace 320.
- a trace 350 depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of three pulses each was applied to the vagus nerve.
- the inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds.
- the VEP is noticeably improved in the trace 350 when compared with the VEP of the trace 340.
- a trace 360 depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of four pulses each was applied to the vagus nerve.
- the inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds.
- the VEP is noticeably improved in the trace 360 when compared with the VEP of the trace 350. Referring to FIG. 4B, the effect of the interpulse interval on the VEP is illustrated.
- Traces 500, 510, 520, 530, and 540 depict the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each, separated by an inter-microburst interval of 4 sec. was applied to the vagus nerve.
- the interpulse intervals were about 40 milliseconds, about 20 milliseconds, about 10 milliseconds, about 6.7 milliseconds, and about 3 milliseconds for the traces 500, 510, 520, 530, and 540, respectively.
- the VEP is barely visible in the trace 500.
- the VEP is noticeably improved in the trace 510 when compared with the VEP of the trace 500.
- the VEP is noticeably improved in the trace 520 when compared with the VEP of the trace 510.
- the VEP is noticeably improved in the trace 530 when compared with the VEP of the trace 520.
- the VEP in the trace 540 is noticeably less than the VEP 534 of the trace 530.
- Traces 600, 610, 620, 630, and 640 depict the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each, the pulses being separated by an interpulse interval of 6.7 milliseconds, was applied to the vagus nerve.
- the inter-microburst intervals corresponded to the microbursts occurring at a microburst frequency of about 10 Hz, about 3 Hz, about 1 Hz, about 0.3 Hz, and about 0.25 Hz for the traces 600, 610, 620, 630, and 640, respectively.
- the VEP is barely visible in the trace 600. Because the inter-microburst internal was sufficiently short, the trace 600 shows a second microburst artifact 606 to the right of the first microburst artifact 602.
- the VEP is noticeably improved in the trace 610 when compared with the VEP of the trace 600.
- the VEP is noticeably improved in the trace 620 when compared with the VEP of the trace 610.
- the VEP is noticeably improved in the trace 630 when compared with the VEP of the trace 620.
- the VEP in the trace 640 is noticeably less than the VEP in the trace 630.
- the VEP is enormously enhanced (resulting in eVEP) and optimized by using a microburst of pulses (two or more, FIG. 4A) at appropriate interpulse intervals (in this case, 6.7 milliseconds was optimal for the first interpulse interval, shown in FIG. 4B) and at a inter-microburst interval (i.e., microburst frequency) that approximates the R-R cycle (i.e., the frequency at which the R wave portion appears in the ECG trace) of the monkey (in this case, about 0.3 Hz, as shown in FIG. 4C).
- a microburst of pulses two or more, FIG. 4A
- appropriate interpulse intervals in this case, 6.7 milliseconds was optimal for the first interpulse interval, shown in FIG. 4B
- a inter-microburst interval i.e., microburst frequency
- 3D-3F and 4A-4C were obtained using a pulse burst including microbursts that were not synchronized with the cardiac cycle.
- the effect of synchronizing the pulse bursts with the cardiac cycle was shown. Specifically, a single pulse was delivered at various times following every third R-wave. The VEP values obtained were then correlated with respiration. With respect to synchronization with the cardiac cycle, the experiments showed that the largest VEP was obtained when the pulse was delivered within 250 milliseconds after the initiation of a breath (which is accompanied by a decrease in the R-R interval). With respect to the delay period, the experiments showed that the greatest improvement in the VEP was obtained when the pulse was delivered about 400 milliseconds after the R-wave.
- the experimental data showed that by timing the pulse properly, an improvement in efficacy on the order of a factor of ten was obtained. Specifically, when the pulse was delivered about 0.5 seconds to about 1.0 second following the initiation of respiration and within 50 milliseconds following the R-wave, the VEP had a peak-to-peak amplitude of about 0.2 mV to about 0.4 mV. In contrast, when the pulse was delivered about 250 milliseconds after the initiation of inspiration and about 400 milliseconds following the R-wave, the VEP had a peak-to-peak amplitude of about 1.2 mV to about 1.4 mV. At maximum, this corresponds to about a seven-fold improvement in the VEP.
- the exogenous electrical signal applied to the vagus nerve may comprise a series of microbursts that each provide an eVEP.
- a microburst duration greater than about 10 milliseconds produces a maximal eVEP in the thalamus of the monkey and an interpulse interval of about 6 milliseconds to about 9 milliseconds produces maximal facilitation by the first pulse of the second pulse.
- a brief microburst of pulses with a total duration of about 10 milliseconds to about 20 milliseconds and having an initial interpulse interval of about 6 milliseconds to about 9 milliseconds and subsequent intervals of similar or longer duration may produce an optimal VEP.
- microbursts of pulses simulate the pattern of naturally occurring action potentials in the small-diameter afferent vagal fibers that elicit the central response that the present enhanced and optimized therapy is most interested in evoking (see below).
- Selection of an appropriate inter-microburst interval to separate one microburst from the next may be performed experimentally, although as previously noted, a period of at least 100 milliseconds (preferably at least 500 milliseconds, and more preferably at least one second) and at least equal to the microburst duration may be desirable.
- the most effective sequence of interpulse intervals will vary with the patient's HRV (cardiac and respiratory timing) and also between individual patients, and thus, in some embodiments, the parameters of the exogenous electrical signal, such as the number of pulses in a microburst, the interpulse interval(s), the inter-microburst interval(s), the duration of the pulse burst, the delay period(s) between each QRS wave and a microburst, the current amplitude, the QRS waves of the cardiac cycle after which a microburst will be applied, the pulse width, and the like may be optimized for each patient.
- HRV cardiac and respiratory timing
- the parameters of the exogenous electrical signal such as the number of pulses in a microburst, the interpulse interval(s), the inter-microburst interval(s), the duration of the pulse burst, the delay period(s) between each QRS wave and a microburst, the current amplitude, the QRS waves of the cardiac cycle after which
- a microburst of 2 or 3 pulses having an interpulse interval of about 5 milliseconds to about 10 milliseconds may be used to approximate the short burst of endogenous post-cardiac activity.
- the inter-microburst interval may be determined empirically by providing microbursts with a steadily decreasing inter-microburst interval until the eVEP begins to decline.
- the interpulse interval varies between the pulses.
- the interpulse interval may increase between each successive pulse in the microburst, simulating the pattern of a decelerating post-synaptic potential, as illustrated in FIG. 1.
- the interpulse intervals may decrease between each successive pulse in the microburst, or may be randomly determined within a pre-selected range, e.g., about 5 milliseconds to about 10 milliseconds.
- the interpulse interval may remain constant between successive pulses in the microburst (i.e., providing a simple pulse train).
- the interpulse intervals may be specified between each successive pair of pulses using the VEP determined by an EEG.
- the optimization is accomplished by using surface electrodes to detect a far-field VEP, originating in the thalamus and other regions of the forebrain, and varying the stimulus parameters to maximize the VEP detected.
- standard EEG recording equipment 700 and a 16-lead or a 25-lead electrode placement 710 of the EEG surface electrodes 712 such as that typically used clinically for recording somatosensory or auditory evoked potentials, enables the VEP present in the patient's forebrain to be detected, using VNS stimulus microburst timing to synchronize averages of about 8 epochs to about 12 epochs.
- the EEG recording equipment 700 may be used to produce continuous EEG waveforms 720 and recordings 730 thereof. By testing the effects of varying the parameters of the exogenous electrical signal, the VEP can be optimized for each patient.
- the exogenous electrical signal used to deliver VNS is optimized in individual patients by selecting stimulus parameters that produce the greatest effect as measured by EEG surface electrodes 740.
- the pulse current amplitude and pulse width is first optimized by measuring the size of the VEP elicited by individual pulses (and not microbursts).
- the number of pulses, interpulse intervals, and inter-microburst intervals are then optimized (using the current amplitude and pulse width determined previously) by measuring the magnitude of the VEP evoked by the microbursts, as well as the effects on de-synchronization in the continuous EEG recordings. It may be desirable to determine the number of pulses first and then determine the interpulse intervals between those pulses.
- the EEG may be used to optimize or tune the signal parameters of the exogenous electrical signal empirically.
- this method provides a safe and non-invasive way to customize the various signal parameters for the patient and/or the treatment of the patient's medical condition.
- the eVEP recorded in the right thalamus and right striatum is significant for the anti-epileptic effects of VNS, whereas the eVEP recorded in the left insular cortex is most significant for the anti-depression effects of VNS.
- the signal parameters of the exogenous electrical signal may be optimized appropriately to achieve an eVEP in the appropriate region of the individual patient's brain. Further, the magnitude of the measured VEP may be appropriately tuned for the patient.
- the optimal exogenous electrical signal parameters for eliciting eVEPs from these two areas may differ. Both eVEPs are identifiable using known EEG recording methods in awake human patients. Therefore, EEG recordings made using these methods may be used to evaluate the eVEP in the appropriate area.
- the EEG recording may be used to collect samples of the eVEP in the appropriate area(s) and those samples may be used easily for a parametric optimization, in a patient suffering from a disorder of the nervous system such as epilepsy or depression.
- the exogenous electrical signal parameters used for HRV-synchronization may be selected based on their effects on the VEP and on the heartbeat-related evoked potential both of which may be measured using known noninvasive EEG recording methods that use EEG electrodes attached to the patient's scalp.
- a pair of traces 810 and 812 correspond to the potential present in the left striatum and left insular cortex and a pair of traces 820 and 822 correspond to the potential present in the left striatum and left insular cortex. While the same traces 810, 812, 820 and 822 depict the potential present in striatum and insular cortex, the potential in the striatum may be distinguished from the potential in the insular cortex by its timing. Experiments have shown that pulses applied to the vagus nerve reach the parafascicular nucleus in the thalamus in about 18 milliseconds and the basal portion of the ventral medial nucleus in about 34 milliseconds.
- the parafascicular nucleus then projects the stimulus to the striatum and the basal portion of the ventral medial nucleus projects the stimulus to the insular cortex. Consequently, the potential evoked by the pulse burst in the striatum will appear in the traces 810, 812, 820 and 822 before the potential evoked in the insular cortex.
- the potential inside the striatum and/or the insular cortex may be observed and the signal parameter used to generate those potentials modified to enhance and/or optimize those potentials. In FIG.
- the strong VEP shown in traces 820 and 822 corresponding to the right thalamus and the right striatum (or basal ganglia) is associated with the anti- epileptic effects of VNS.
- distinguishing the right thalamus from the right insular cortex may be accomplished by analyzing the timing of the eVEP observed in the traces 820 and 822.
- the strong VEP shown in traces 810 and 812 corresponding to the left thalamus and left insular cortex is associated with the anti- depression effects of VNS.
- Traces 830 and 832 in the central portion of the EEG depict a weak VEP in the thalamus.
- FIG. 7 illustrates one method of variable programming of the electrical signal generator 200 to optimize the eVEP in the right thalamus and striatum for epileptic patients, and in the left insula for patients suffering from depression.
- a computer 900 may be coupled to and used to program the computer-controlled programming wand 800.
- the programming wand 800 may use radio frequency telemetry to communicate with the electrical signal generator 200 and program the burst duration, number of pulses in a microburst, interpulse interval(s), pulse frequency, microburst duration, inter-microburst interval, pulse width, and current amplitude of the exogenous electrical signal delivered by the electrical signal generator 200 to the vagus nerve of the patient.
- programming may be performed periodically or as needed on an implanted electrical signal generator 200. This provides the ability to continually optimize and change the exogenous electrical signal delivered by the electrical signal generator 200 depending on the EEG, and to respond to changes therein. Therefore, the present method of using one or more of the above referenced techniques, alone or in combination, significantly enhances and/or optimizes currently available VNS therapies.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physiology (AREA)
- Biophysics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Developmental Disabilities (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pulmonology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Electrotherapy Devices (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Abstract
An implanted electrical signal generator delivers a novel exogenous electrical signal to a vagus nerve of a patient. The vagus nerve conducts action potentials originating in the heart and lungs to various structures of the brain, thereby eliciting a vagal evoked potential in those structures. The exogenous electrical signal simulates and/or augments the endogenous afferent activity originating from the heart and/or lungs of the patient, thereby enhancing the vagal evoked potential in the various structures of the brain. The exogenous electrical signal includes a series of electrical pulses organized or patterned into a series of microbursts including 2 to 20 pulses each. No pulses are sent between the microbursts. Each of the microbursts may be synchronized with the QRS wave portion of an ECG. The enhanced vagal evoked potential in the various structures of the brain may be used to treat various medical conditions including epilepsy and depression.
Description
VAGUS NERVE STIMULATION METHOD
CROSS REFERENCE TO RELATED APPLICATION(S) This application claims the benefit of U.S. Provisional Application No.
60/787,680, filed March 29, 2006.
The United States patent application entitled "Synchronization Of Vagus Nerve Stimulation With The Cardiac Cycle Of A Patient" by Arthur D. Craig and filed concurrently herewith is hereby incorporated herein by reference. The United States patent application entitled "Microburst Electrical
Stimulation Of Cranial Nerves For The Treatment Of Medical Conditions," by Arthur D. Craig and filed concurrently herewith is hereby incorporated herein by reference.
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention is directed generally to neurostimulation of the vagus nerve, and more particularly to an improved apparatus and method for vagus nerve stimulation therapy using heart rate variability synchronization, patterned electrical pulses inside a pulse burst, and electroencephalogram ("EEG") based optimization.
Description of the Related Art
Vagus nerve stimulation ("VNS") (for example, VNS Therapy™ by Cyberonics, Inc.) is an FDA-approved method for alleviating treatment-resistant epilepsy and depression.
Vagus nerve stimulation was initially developed and approved by the FDA for the treatment of refractory partial onset epilepsy. Recently, it has been reported that the use of VNS in human patients with epilepsy is associated with an improvement in mood. As a consequence, VNS has also been approved as a treatment for refractory depression (treatment resistant depression).
VNS typically involves implanting a nerve stimulating electrode on the left or right vagus nerve in the neck. The electrode is connected to a subcutaneous pacemaker-like control unit that generates an electrical nerve stimulating signal. A
Vagus Nerve Stimulator ("VNS stimulator") is an example of an implantable stopwatch- sized, pace maker- 1 ike control unit device configured to electrically stimulate the vagus nerve leading to the brain.
Conventional VNS is generally applied every 5 minutes in a 7 second to one minute burst (see FIG. 3A for a portion of an exemplary burst) including a pulse train of uniformly spaced apart pulses having a pulse current amplitude of about 0.5 mA to about 2.0 mA). The pulses are delivered at about 20 Hz to about 50 Hz. Each of the pulses may have a width of about 0.5 milliseconds. VNS is currently approved to treat epileptic seizures and depression when drugs have been ineffective. Consequently, a need exists for methods of delivering electrical stimulation to the vagus nerve. Further, a need exists for improved electrical signals that increase the efficacy of VNS.
SUMMARY OF THE INVENTION In one embodiment, the invention includes a method of treating a medical condition by detecting a portion of the QRS wave of the patient's cardiac signal and after detecting the portion of the QRS wave, delivering a microburst comprising 2 to 20 electrical pulses to the patient's vagus nerve. Each of the microbursts may have duration of less than about 100 milliseconds. In particular embodiments, the interpulse intervals separating the pulses are about 3 milliseconds to about 12 milliseconds. In alternate embodiments, the interpulse intervals are less than about 40 milliseconds. In various embodiments, the sum of the interpulse intervals is less than about 40 milliseconds, and in further embodiments, less than about 60 milliseconds. In further embodiments, the method includes waiting a predetermined delay period after the detection of the portion of the QRS wave before generating the microburst.
In another embodiment, the invention includes an exogenous electrical signal delivered to a patient's vagus nerve and adapted to treat a medical condition present in the patient by enhancing the vagal evoked potential in the patient's brain. The exogenous electrical signal includes a series of microbursts each having about 2 to about 20 electrical pulses. In some embodiments, the exogenous electrical signal includes a series of microbursts each having a duration less than about one second. The invention also includes an implantable device configured to apply the inventive exogenous electrical signal.
In further embodiments, the microbursts of the exogenous electrical signal may be synchronized with the R wave portion of the patient's cardiac cycle. In particular embodiments, each of the microbursts of the exogenous electrical signal occur after a selected R wave portion. In various embodiments, each of the microbursts occurs less than about 1000 milliseconds after the selected R wave portion. The pulses of the microbursts may be spaced to simulate the endogenous afferent activity occurring at a particular time in the cardiac cycle. Further, each of the microbursts may be delayed relative to the selected R wave portion to simulate the endogenous afferent activity occurring at a particular time in the cardiac cycle. In various embodiments, the delay has a duration less than about 500 milliseconds. In further embodiments, the delay has a duration less than about 1000 milliseconds.
In various embodiments, each of the microbursts occurs after an R-R interval (i.e., the amount of time between two successive R wave portions in the cardiac signal) having a duration that is shorter than the duration of the previous R-R interval. In further embodiments, the microbursts are delivered to the vagus nerve after the R wave portions occurring during inspiration but not after the R wave portions occurring during expiration.
The invention also includes a method of customizing the exogenous electrical signal to elicit a desired vagal evoked potential in a selected structure of the brain associated with a medical condition. The method includes determining a value of a signal parameter (e.g., pulse width, pulse frequency, an interpulse interval between two of the pulses of the microburst, microburst frequency, a number of microbursts of the series of microburst, a duration of the electrical signal, a number of pulses in the microbursts, etc.), generating an electrical signal having a series of microbursts of 2 to 20 electrical pulses each according to the signal parameter, delivering the electrical signal to the patient's vagus nerve, analyzing an EEG of the patient's brain created during the delivery of the electrical signal to determine the vagal evoked potential observed in the selected structure of the brain, and modifying the value of the signal parameter based on the vagal evoked potential observed in the selected structure of the brain to modify the vagal evoked potential observed therein. In various embodiments, the selected structure of the brain includes the thalamus, striatum, and/or insular cortex.
Embodiments of the invention also include a computer readable medium having computer executable components for detecting the QRS wave portion of the
cardiac cycle, generating a microburst, and delivering the microburst to the vagus nerve of a patient in response to the detection of the QRS wave portion of the patient's cardiac cycle.
The invention also includes embodiments wherein the patient manually triggers the generation and delivery of the inventive exogenous electrical signal to his/her vagus nerve.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)
Figure 1 illustrates a portion of an ECG trace located above a portion of a trace illustrating an exogenous electrical signal patterned into microbursts that are synchronized with the QRS wave portion of the ECG trace. Each of the microbursts begins after a delay period following the QRS wave portion of the ECG trace.
Figure 2A illustrates a conventional electrical signal generator that may be modified to deliver an exogenous electrical signal constructed according to the present invention.
Figure 2B is a block diagram illustrating various components of the electrical signal generator of Figure 2A.
Figure 3A is a trace illustrating an exemplary conventional VNS exogenous electrical signal having a series of pulses. Figure 3B is a trace of the potential measured in a monkey's thalamus while a portion of the conventional pulse burst of Figure 3A was applied to the vagus nerve of the monkey.
Figure 3C is a trace illustrating an exemplary embodiment of an exogenous electrical signal constructed according to the present invention. Figure 3D is a trace illustrating the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of four pulses each was applied to the vagus nerve. The inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds.
Figure 3E provides nine exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals were applied to the vagus nerve of the monkey. Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve. Each of the exogenous electrical signals included a series of microbursts having a selected number of pulses each. The
pulses of the microbursts of the exogenous electrical signals of the topmost row have an interpulse interval of 3 milliseconds. The pulses of the microbursts of the exogenous electrical signals of the middle row have an interpulse interval of 6 milliseconds. The pulses of the microbursts of the exogenous electrical signals of the bottom row have an interpulse interval of 9 milliseconds.
Figure 3F provides three exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals were applied to the vagus nerve of the monkey. Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve. All of the exogenous electrical signals included a series of microbursts having three pulses each. The pulses had an interpulse interval of 9 milliseconds. The exogenous electrical signal used to generate the leftmost trace included microbursts separated by an inter-microburst interval of about 6 seconds. The exogenous electrical signal used to generate the middle trace included microbursts separated by an inter-microburst interval of about 2 seconds. The exogenous electrical signal used to generate the rightmost trace included microbursts separated by an inter-microburst interval of about 0.5 seconds.
Figure 4A provides four exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals were applied to the vagus nerve of the monkey. For all of the exogenous electrical signals, the inter- microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds.
A topmost trace illustrates the average potential (after 20 pulses) measured in the monkey thalamus while a pulse burst having a series of uniformly spaced apart pulses was applied to the monkey's vagus nerve. The spacing between the pulses was about 4 seconds.
A second trace from the top depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each was applied to the vagus nerve. A third trace from the top depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of three pulses each was applied to the vagus nerve.
The bottommost trace depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of four pulses each was applied to the vagus nerve.
Figure 4B provides five exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals including microbursts having two pulses each, the microbursts being separated by an inter-microburst interval of about 4 seconds, were applied to the vagus nerve of the monkey. Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve.
The interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 40 milliseconds in the topmost trace.
The interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 20 milliseconds in the trace second from the top. The interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 10 milliseconds in the trace third from the top.
The interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 6.7 milliseconds in the trace fourth from the top.
The interpulse interval between the pulses of the microbursts of the exogenous electrical signal was about 3 milliseconds in the bottommost trace.
Figure 4C provides five exemplary traces of the potential measured inside a monkey's thalamus while various exogenous electrical signals including microbursts having two pulses each, the pulses of each of the microbursts being separated by an interpulse interval of about 6.7 seconds, were applied to the vagus nerve of the monkey. Each of the traces illustrates the average potential (after 20 microbursts) measured in the monkey thalamus while the exogenous electrical signals was applied to the monkey's vagus nerve.
The inter-microburst interval between the microbursts of the exogenous electrical signal used in the topmost trace corresponded to the microbursts occurring at a microburst frequency of about 10 Hz.
The inter-microburst interval between the microbursts of the exogenous electrical signal used in the trace second from the top corresponded to the microbursts occurring at a microburst frequency of about 3 Hz.
The inter-microburst interval between the microbursts of the exogenous electrical signal used in the trace third from the top corresponded to the microbursts occurring at a microburst frequency of about 1 Hz.
The inter-microburst interval between the microbursts of the exogenous electrical signal used in the trace fourth from the top corresponded to the microbursts occurring at a microburst frequency of about 0.3 Hz.
The inter-microburst interval between the microbursts of the exogenous electrical signal used in the bottommost trace corresponded to the microbursts occurring at a microburst frequency of about 0.25 Hz. Figure 5 illustrates a system for using a conventional EEG device to optimize an exogenous electrical signal used for VNS stimulation according to the present disclosure.
Figure 6 provides an exemplary EEG illustrating the vagal evoked potential elicited by an exogenous electrical signal constructed according to the present invention.
Figure 7 illustrates an exemplary embodiment of an electrical signal generator programming and/or reprogramming device for use with the electrical signal generator of Figure 2A-2B.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides novel techniques, alone or in combination, to improve the efficacy of VNS used in the treatment of a variety of medical conditions, including disorders of the nervous system, such as epilepsy and depression. The following disclosure describes various embodiments of a novel method and its associated apparatus for improving VNS therapies. According to the present disclosure, these novel techniques are particularly useful for treating epilepsy and depression. However, it is envisioned that these same novel techniques may be used to treat a variety of disorders and conditions that include a physiological relationship to the nervous system, such as neuropsychiatric disorders, eating disorders/obesity, traumatic brain injury/coma, addiction disorders, dementia, sleep disorders, pain, migraine, endocrine/pancreatic disorders (including but not limited to diabetes), motility disorders, hypertension, congestive heart failure/cardiac capillary growth, hearing disorders, angina, syncope, vocal cord disorders, thyroid disorders, pulmonary disorders, and reproductive endocrine disorders (including infertility). Thus, based on
the aforementioned relationship to the nervous system, these disorders and conditions, including epilepsy and depression, are collectively referred to herein as disorders of the nervous system, even if not conventionally described as such.
One of the novel techniques includes synchronizing portions of an exogenous electrical signal with the endogenous afferent activity of the vagus nerve, primarily the endogenous afferent activity originating from receptors in the heart and lungs. Stimulating the vagus nerve in synchrony with endogenous vagal rhythms, in particular with cardiac cycle and heart rate variability (HRV), enhances therapeutic efficacy of VNS. In the prior art, the exogenous electrical signal applied to the vagus nerve during conventional VNS is often referred to as a pulse burst. The pulse burst typically includes a series of uniformly spaced apart substantially identical pulses, i.e., a simple pulse train. The VNS applied to treat disorders of the nervous system may include multiple pulse bursts separated by an interburst delay. An individual pulse burst may be triggered automatically or manually. In many prior art devices, a pulse burst may be triggered by the detection of a medical event such as a seizure, or may be triggered manually by the user or a medical professional. Alternatively, pulse bursts may occur at regular intervals separated by a predetermined interburst delay. Typically, the interburst delay is about five minutes, 30 minutes, or 60 minutes.
The pulses of the conventional VNS pulse bursts are applied asynchronously, i.e., asynchronous with both the cardiac and lung cycles. As mentioned above, conventional VNS is generally applied every 5 minutes in a 7 second to one minute pulse burst (see FIG. 3A for a portion of an exemplary burst) of uniformly spaced apart pulses having an pulse current amplitude of about 0.5 mA to about 2.0 mA. The pulses are delivered at about 20 Hz to about 50 Hz. Each of the pulses may have a width of about 0.5 milliseconds. While monophasic pulses are generally used, biphasic pulses may also be used. As used herein, the term "pulses" refers to both monophasic and biphasic pulses. In the present invention, the pulses within a pulse burst are patterned or otherwise organized to improve and/or optimize stimulation of the vagus nerve and/or structures of the brain in communication therewith. The natural endogenous afferent activity in the left and right vagus nerves predominantly occurs immediately following each cardiac contraction and during each inspiration. Further, the timing of the
endogenous afferent activity in the left and right vagus nerves varies with heart rate, breathing rate, and emotional state. However, because the left and right vagus nerves innervate different portions of the heart, the timing of the afferent activity in the left vagus nerve may differ from the timing of the afferent activity in the right vagus nerve. Consequently, the patterning of the pulse burst may be different for the right and left vagus nerves. As is appreciated by those of ordinary skill in the art, the pulse burst is generally applied to the left vagus nerve because VNS stimulators implanted on the right side applying a pulse burst to the right vagus nerve are associated with an increase in patient mortality. As used herein, the term "vagus nerve" may refer to either the left or right vagus nerve.
According to one aspect of the present invention, a novel exogenous electrical signal is applied to the vagus nerve. The novel exogenous electrical signal is configured to augment the natural endogenous afferent activity in the vagus nerve by timing the pulses within a pulse burst in an improved and more effective manner. In particular embodiments, as will be described in detail below, the pulses within the pulse burst may be organized into sub-bursts or microbursts (each having about 2 to about 20 pulses) that are synchronized with the endogenous afferent activity in the vagus nerve to augment the endogenous afferent activity therein.
Referring to FIG. 1 , a trace 100 of a portion of an exemplary embodiment of the novel exogenous electrical signal is provided. Located above the trace 100 in FIG. 1 , an exemplary electrocardiogram (ECG) trace 120 depicting cardiac activity detected by an electrocardiograph (not shown) is provided. The novel exogenous electrical signal includes a pulse burst 130 organized into a series of microbursts 170. Each of the microbursts 170 is synchronized with a portion of the cardiac cycle depicted in the ECG trace 120. In particular, each of the microbursts 170 is synchronized with the QRS wave portion 174 of the ECG trace 120, so that endogenous cardiac-related and respiration-related vagal afferent activity is augmented by the microbursts 170 of the exogenous electrical signal.
As illustrated in FIG. 1 , each of the microbursts 170 may be triggered by an R-wave portion 176 of the QRS wave portion 174. Without being bound by theory, it is believed that synchronizing the application of the microbursts 170 of the exogenous electrical signal to the vagus nerve with the detection of the R-wave portion 176 of the patient's cardiac cycle may increase the efficacy of VNS therapy by entraining the exogenous electrical signal with the endogenous cyclic facilitation of central vagal
afferent pathways. Each of the microbursts 170 begins after the elapse of a delay period, which comprises a variable time period that may range, e.g., from about 10 milliseconds to about 1000 milliseconds following detection of the R-wave portion 176. In various embodiments, the delay period may be less than about 10 milliseconds. Further, in some embodiments, the delay period may be about 10 milliseconds to about 500 milliseconds or about 10 milliseconds to about 800 milliseconds. In further embodiments, the delay period is less than 1000 milliseconds. In other embodiments, the delay period may be omitted. Each of the delay periods may comprise a predetermined duration such as about 10 milliseconds, or may comprise a random time duration within a predetermined minimum and maximum time duration, e.g., a random time duration from about 10 milliseconds to about 1000 milliseconds. Further, as will be described below, the duration of the delay period preceding each microburst 170 may be determined empirically.
For example, the leftmost (first) microburst 170 begins after a delay period "D1 ," the next (or second) microburst 170 begins after a delay period "D2," and the third microburst 170 begins after a delay period "D3." The delay period "D1 " may be shorter than the delay periods "D2" and "D3." Additionally, the delay period "D2" may be shorter than the delay period "D3." In alternate embodiments, the delay periods "D1 ," "D2," and "D3" may be substantially identical. In further embodiments, the delay period "D1 ," may be larger than delay period "D2," which may be larger than delay period "D3." Embodiments wherein each of the delay periods "D1 ," "D2," and "D3" is selected randomly within a specified range of delay values or determined empirically are also within the scope of the present invention. As will be appreciated by those of skill in the art, still further embodiments of the present invention may include a variety of delay period combinations that can be identified and implemented by routine experimentation. Each of these is considered to be within the scope of the present invention. While three delay periods have been described with respect to Fig. 1 , it is apparent to those of ordinary skill that a delay period may precede each microburst of a pulse burst and the duration of the delay period may be determined empirically or randomly.
In various embodiments, the synchronization of the exogenous electrical signal further comprises not providing pulses during selected portions of the cardiac cycle, such as periods in the opposite half of the cardiac and respiratory duty cycles, when the central pathways are inhibited. Again without being bound by theory, it is
believed that pulses applied to the vagus nerve during the opposite half of the cardiac and respiratory duty cycles are less effective because endogenous signals in this part of the cardiac and/or respiratory cycles are less significant, in terms of their information content, for modulating those portions of the brain relevant to homeostasis mechanisms implicated in medical conditions such as epilepsy and depression. Thus, at least a portion of the asynchronous exogenous electrical signal delivered by current stimulation algorithms, such as conventional VNS, may be therapeutically irrelevant.
Because the exogenous electrical signal is typically delivered by an implanted device powered by a battery, the delivery of irrelevant signals may result in unnecessary battery depletion. Further, the pulse burst sometimes causes the patient's vocal cords to contract causing his/her voice to become horse, which is uncomfortable and makes talking difficult. Sometimes, the pulse burst causes neck pain and may cause cardiac problems. Therefore, reducing the number of pulses may contribute to patient comfort and/or safety. Synchronizing the microbursts 170 of the exogenous electrical signal with each individual QRS wave portion 174 also tracks the natural variability in vagal afferent activity that occurs during breathing and emotional shifts. This heart rate variability (HRV) is a function of respiration and efferent sympathovagal tone. During inspiration, the heart rate accelerates and during expiration it decelerates. Thus, an R- R interval (i.e., the time that elapses between successive R wave portions 176) appearing in the ECG is shorter during inspiration and longer during expiration, producing HRV. HRV is also known as respiratory sinus arrhythmia. Additionally, it is well established that a larger HRV is associated with greater physical health, including greater immune function, lower risk of cardiac arrhythmia, and better mood, than a smaller HRV.
HRV is greatly increased during meditation, and HRV is increased easily by slow, paced breathing. Synchronizing the microbursts 170 of the exogenous electrical signal with each QRS wave portion 174 of the cardiac cycle utilizes and accentuates the positive association of HRV with overall bodily health. Further, it helps ensure that the microbursts 170 of the exogenous electrical signal are synchronized with variances in the cardiac cycle. Consequently, it may be beneficial for the patient to begin paced breathing during the pulse burst. Further, it may improve the efficacy of the exogenous electrical signal if the pulse burst is triggered while the patient is performing paced breathing.
Referring to FIG. 2A-2B, a suitable electrical signal generator 200, such as a VNS stimulator, known in the art has one or more electrodes 220A and 220B coupled to the vagus nerve for delivering electrical pulses thereto. In embodiments wherein the microbursts of the exogenous electrical signal are synchronized with the cardiac cycle, optionally, the electrical signal generator 200 has the capacity to detect cardiac signals and produce an ECG trace for the purpose of avoiding the deliverance of conventional VNS in the event of cardiac arrest. In other words, the suitable electrical signal generator 200 for use with the present invention may include one or more sensors, such as sensing electrodes 210A and 210B positioned to detect cardiac electrical signals, and the onboard capability of analyzing those signals. In particular, the electrical signal generator 200 may be capable of identifying the R wave portion of the cardiac signal. In alternative embodiments, the sensor(s) may include an acoustic device configured to detect the cardiac cycle.
In embodiments wherein the microbursts of the exogenous electrical signal are synchronized with the cardiac cycle, the electrical signal generator 200 may be modified or programmed to deliver the novel exogenous electrical signal. The modifications include replacing a more common open-loop or non-feedback stimulation system with a feedback system utilizing one or more sensing electrodes 210A and 21 OB to detect the QRS wave portion 174 of the ECG trace 120 (see FIG. 1 ). The modification of the electrical signal generator 200 is effected by programming the electrical signal generator 200 to initiate a microburst 170 after the elapse of the delay period, such as delay period "D1 ", delay period "D2", or delay period "D3," following the detection of the QRS wave portion 174. Again, while three exemplary delay periods have been described, a delay period may precede each microburst and such embodiments are within the scope of the present invention. Further, embodiments in which no delay period precedes a microburst are also within scope of the present invention. As is apparent to those of ordinary skill in the art, embodiments of the electrical signal generator 200 that have the feedback system for detecting the QRS wave portion 174 without modification are also within the scope of the present invention.
FIG. 2B is a block diagram of various components of the electrical signal generator 200. The electrical signal generator 200 may include a programmable central processing unit (CPU) 230 which may be implemented by any known technology, such as a microprocessor, microcontroller, application-specific integrated
circuit (ASIC), digital signal processor (DSP), or the like. The CPU 230 may be integrated into an electrical circuit, such as a conventional circuit board, that supplies power to the CPU 230. The CPU 230 may include internal memory or memory 240 may be coupled thereto. The memory 240 is a computer readable medium that includes instructions or computer executable components that are executed by the CPU 230. The memory 240 may be coupled to the CPU 230 by an internal bus 250.
The memory 240 may comprise random access memory (RAM) and readonly memory (ROM). The memory 240 contains instructions and data that control the operation of the CPU 230. The memory 240 may also include a basic input/output system (BIOS), which contains the basic routines that help transfer information between elements within the electrical signal generator 200. The present invention is not limited by the specific hardware component(s) used to implement the CPU 230 or memory 240 components of the electrical signal generator 200.
The electrical signal generator 200 may also include an external device interface 260 permitting the user or a medical professional to enter control commands, such as a command triggering the delivery of the novel exogenous electrical signal, commands providing new instructions to be executed by the CPU 230, commands changing parameters related to the novel exogenous electrical signal delivered by the electrical signal generator 200, and the like, into the electrical signal generator 200. The external device interface 260 may include a wireless user input device. The external device interface 260 may include an antenna (not shown) for receiving a command signal, such as a radio frequency (RF) signal, from a wireless user input device such as a computer-controlled programming wand 800 (see FIG. 7). The electrical signal generator 200 may also include software components for interpreting the command signal and executing control commands included in the command signal. These software components may be stored in the memory 240.
The electrical signal generator 200 includes a cardiac signal interface 212 coupled to sensing electrodes 210A and 210B for receiving cardiac electrical signals. The cardiac signal interface 212 may include any standard electrical interface known in the art for connecting a signal carrying wire to a conventional circuit board as well as any components capable of communicating a low voltage time varying signal received from the sensing electrodes 21 OA and 21 OB through an internal bus 214 to the CPU 230. The cardiac signal interface 212 may include hardware components such as
memory as well as standard signal processing components such as an analog to digital converter, amplifiers, filters, and the like.
The electrical signal generator 200 includes an exogenous electrical signal interface 222 coupled to electrodes 220A and 220B for delivering the exogenous electrical signal to the vagus nerve. The exogenous electrical signal interface 222 may include any standard electrical interface known in the art for connecting a signal carrying wire to a conventional circuit board as well as any components capable of communicating a low voltage time varying signal generated by the CPU 230 or a signal generating device controlled by the CPU 230 to the electrodes 220A and 220B through an internal bus 252. The exogenous electrical signal interface 222 may include hardware components such as memory as well as standard signal processing components such as a digital to analog converter, amplifiers, filters, and the like.
The various components of the electrical signal generator 200 may be coupled together by the internal buses 214, 250, 252, and 254. Each of the internal buses 214, 250, 252, and 254 may be constructed using a data bus, control bus, power bus, I/O bus, and the like.
The electrical signal generator 200 may include instructions 280 executable by the CPU 230 for processing and/or analyzing the cardiac electrical signals received by the sensing electrodes 210A and 210B. Additionally, the electrical signal generator 200 may include instructions 280 executable by the CPU 230 for generating an exogenous electrical signal delivered to the vagus nerve by the electrodes 220A and 220B. These instructions may include computer readable software components or modules stored in the memory 240. The instructions 280 may include a Cardiac Signal Monitoring Module 282 that generates a traditional ECG trace from the cardiac electrical signals. The Cardiac Signal Monitoring Module 282 may record the ECG trace in the memory 240.
As is appreciated by those of ordinary skill in the art, generating an ECG trace from an analog cardiac electrical signal may require digital or analog hardware components, such as an analog to digital converter, amplifiers, filters, and the like and such embodiments are within the scope of the present invention. In one embodiment, some or all of these components may be included in the cardiac signal interface 212. In an alternate embodiment, some or all of these components may be implemented by software instructions included in the Cardiac Signal Monitoring Module 282. The
Cardiac Signal Monitoring Module 282 may include any method known in the art for generating an ECG trace from a time varying voltage signal.
As mentioned above, the unmodified electrical signal generator 200 monitors cardiac electrical signals for the purposes of detecting a cardiac arrest. The Cardiac Signal Monitoring Module 282 may be modified to include instructions for detecting or identifying the R wave portion of the ECG trace. The R wave portion of the ECG trace may be detected using any method known in the art. While the electrical signal generator 200 has been described as having the Cardiac Signal Monitoring Module 282, embodiments in which the functionality of the Cardiac Signal Monitoring Module 282 is performed by more than one software component are within the scope of the present invention.
The unmodified electrical signal generator 200 generates the exogenous electrical signal used by conventional VNS. The instructions 280 include a Signal Generation Module 284 for instructing the CPU 230 how and when to generate the conventional VNS exogenous electrical signal and deliver it to the vagus nerve via the electrodes 220A and 220B. The Signal Generation Module 284 may be modified to generate the inventive novel exogenous electrical signal. Specifically, the Signal Generation Module 284 may be modified to include instructions directing the CPU 230 to synchronize the microbursts of the exogenous electrical signal with the R wave portion of the ECG trace. The Signal Generation Module 284 may determine the values of the various parameters used to define the novel exogenous electrical signal based on simulating the endogenous afferent activity of the vagus nerve as described herein. Alternatively, the values of the various parameters may be stored in the memory 240 and used by the Signal Generation Module 284 to generate the novel exogenous electrical signal. The various parameters may be entered into the memory 240 by the external device interface 260 which permits the user or medical professional to enter control commands, including commands changing parameters related to the novel exogenous electrical signal delivered by the electrical signal generator 200, and the like, into the electrical signal generator 200. While the electrical signal generator 200 has been described as having the Signal Generation Module 284, embodiments in which the functionality of the Signal Generation Module 284 is performed by more than one software component are within the scope of the present invention.
Examples of suitable electrical signal generators for use with the present invention include a model 103 VNS stimulator (formally referred to as the Gen39) produced by Cyberonics, Inc. (Houston, TX), model 104 VNS stimulator also produced by Cyberonics, Inc., and the like. The analog recording and ECG recognition capacity of these VNS stimulators enable their onboard processor to be programmed to produce pulse bursts of vagal stimulation having the desired parameters at variable delay periods following the detection of the R-wave of the ECG. The delay periods may comprise a predetermined, programmable duration such as about 10 milliseconds, or may comprise a random time duration within a predetermined programmable minimum and maximum time duration, e.g., a random time duration from about 10 milliseconds to about 1000 milliseconds. The predetermined, programmable duration(s) of the delay period(s) may be determined empirically using methods described below.
While a relatively sophisticated embodiment of the electrical signal generator 200 is described above, those of ordinary skill appreciate that simpler devices, such as a device configured to deliver the exogenous electrical signal asynchronously (i.e., an exogenous electrical signal having microbursts that are not synchronized with the cardiac cycle) are also within the scope of the present invention. The electrical signal generator 200 may provide an asynchronous exogenous electrical signal having microbursts spaced at regular or variable intervals. For example, the microbursts may occur at least every 100 milliseconds or at the microburst frequency of about 0.25 Hz to about 10 Hz. The pulses within the microbursts may be spaced at regular or variable intervals. Further, less sophisticated embodiments of the electrical signal generator 200 include electrical signal generators that are pre-programmed with the exogenous electrical signal parameters (e.g., pulse width, pulse frequency, interpulse interval(s), microburst frequency, number of pulses in the microbursts, etc.) before implementation and may retain those pre-programmed parameter values throughout the functional life of the electrical signal generator. Alternatively, electrical signal generators configured to generate an asynchronous exogenous electrical signal may be programmable after implementation. For example, the computer-controlled programming wand 800 (see FIG. 7) may be used in the manner described above to program such electrical signal generators. As is readily apparent to those of ordinary skill, the present invention is not limited by the particular electrical signal generator used to generate the inventive exogenous electrical signal.
In one aspect, the microbursts of the exogenous electrical signal may be delivered following every detected R-wave occurring within a predetermined pulse burst period, i.e., the period of time during which the exogenous electrical signal is generated. In another embodiment, the microbursts may be applied to the vagus nerve only during the inspiratory phase. This may be implemented by programming the electrical signal generator 200 to apply a microburst only on the shortening R-R intervals during HRV, i.e., only on an R-wave having an R-R interval less than the preceding R-R interval, or less than a moving average for several R-R intervals, e.g., less than a 5 or 10 R-R interval moving average. In further embodiments, the electrical signal generator 200 may include a sensor, such as a strain gauge or acoustic device, that detects various biometric parameters such as heartbeat and the respiratory cycle. For example, a strain gauge may be used to determine inspiration is occurring by identifying when the chest is expanding. The invention is not limited by the method used to determine inspiration is occurring, the R-R interval, and/or whether the R-R intervals are shortening for the purposes of determining inspiration is occurring.
The timing parameters defining how the microbursts of the exogenous electrical signal are synchronized with the cardiac cycle for maximal therapeutic efficacy may be determined empirically, and according to particular embodiments, are individually optimized for each patient (as described below). In alternate embodiments, patients may perform paced breathing, e.g., taking a breath at a frequency of about 0.1 Hz, during periods when the exogenous electrical signal is being delivered to the vagus nerve, to facilitate or increase the amount of HRV.
In further embodiments, the various parameters of the cardiac cycle synchronized exogenous electrical signal may be varied, including without limitation the duration of the pulse burst, the delay period(s) following R-wave detection, the number of pulses comprising a microburst, the interpulse interval (i.e., the amount of time separating one pulse from an adjacent pulse), and the inter-microburst interval (i.e., the amount of time between successive microbursts). Further, these parameters may be selectively associated with particular R-waves of the respiratory cycle, depending on the length of each preceding R-R-interval. In various embodiments, these parameters are empirically optimized for each patient.
In another aspect of the present invention, a method of providing an exogenous electrical signal capable of inducing a much larger vagal evoked potential (VEP) than that induced by conventional VNS is provided. The exogenous electrical
signal provided to the vagus nerve comprises a pulse burst including a series of microbursts. As described above the inter-microburst interval may be determined by the cardiac cycle.
An example of a portion of a pulse burst 300 used in conventional VNS may be viewed in FIG. 3A. The pulse burst 300 includes a plurality of uniformly spaced apart pulses 302 occurring about every 20 milliseconds to about every 50 milliseconds, i.e., occurring at a frequency of about 20 Hz to about 50 Hz. A conventional pulse burst, such as pulse burst 300 may have a pulse burst duration of about 7 seconds to about 60 seconds (resulting in a pulse burst having from about 140 to about 3000 pulses or more). Each pulse 302 may have a width or duration of about 50 microseconds to about 1000 microseconds (μsec) and a pulse current of about 0.1 mA to about 8 mA.
The pulse burst 300 may be separated from a pulse burst identical to pulse burst 300 by an interburst interval of about 5 min. Sometimes, an interburst interval of about 30 min. or about 60 min. is used. In further implementations, the pulse burst 300 is triggered by the onset of a medical event, such as a seizure, or is triggered by the user or a medical professional. In such embodiments, the interburst interval varies.
FIG. 3B provides a trace 304 of the potential measured in the monkey thalamus while the conventional pulse burst 300 (see FIG. 3A) of uniformly spaced pulses 302 having an interpulse interval of 4 seconds was applied to the vagus nerve. The trace 304 shows the potential inside the thalamus immediately after each of the pulses 302 is delivered to the vagus nerve. An increased VEP 305 occurs after the first pulse 302. However, as illustrated by FIG. 3B, little to no increased VEP is observed after the successive pulses 302 in the series. The average potential inside the thalamus observed over 20 pulses is provided by a topmost trace 320 in FIG. 4A. The VEP is the difference between a minimum average potential in the trace 320 observed after an averaged pulse portion 303 of the trace 320 and a maximum average potential in the trace 320 observed after the averaged pulse portion 303 of the trace 320. However, as illustrated in the trace 320, the minimum and the maximum potentials are not clearly identifiable.
Referring to FIG. 3C, a portion of a pulse burst 400 of the exogenous electrical signal constructed in accordance with the present invention is provided. As is apparent to those of ordinary skill, unlike the uniformly spaced pulses 302 of the pulse
burst 300, the pulses 402 and 404 of the pulse burst 400 are patterned or structured within the pulse burst 400. Specifically, the pulses 402 and 404 are arranged into microbursts 41 OA, 41 OB, and 41 OC. In the embodiment depicted in FIG. 3C, each of the microbursts 41 OA, 41 OB, and 41 OC includes the pulse 402 followed by the pulse 404. Each of the individual pulses 402 and 404 in the pulse burst 400 resemble the pulses 302 of the conventional VNS pulse burst 300 and have a pulse width of about 50 microseconds to about 1000 microseconds (μsec) and a pulse current of about 0.25 mA to about 8 mA. In particular embodiments, the pulse current is less than about 2 mA. While the individual pulses 402 and 404 in the pulse burst 400 resemble the pulses 302 of the conventional VNS pulse burst 300 (i.e., each has a pulse width of about 50 microseconds to about 1000 microseconds (μsec) and a pulse current of about 0.25 mA to about 8 mA) the number of pulses 402 and 404 in the pulse burst 400 is markedly smaller than the number of pulses 302 in the pulse burst 300, assuming the pulse burst 400 has the same duration as the pulse burst 300. As mentioned above, the conventional pulse burst 300 may have a pulse burst duration of about 7 seconds to about 60 seconds and a pulse frequency of about 20 Hz to about 50 Hz, resulting in a pulse burst having from about 140 to about 3000 pulses or more. If the pulse burst 400 has a duration of about 7 seconds to about 60 seconds, and the microbursts are delivered every 0.5 seconds, roughly corresponding to the interval between heart beats during inspiration, the pulse burst 400 will have about 30 pulses to about 242 pulses.
As mentioned above, reducing the number of pulses delivered to the vagus nerve may help prolong battery life as well as improve patient comfort and safety. Further, patterning the pulses of the pulse burst 400 into microbursts, such as microbursts 41 OA, 41 OB, and 41 OC increases the VEP observed in the brain. Because the VEP is increased, the current amplitude may be reduced, further increasing patient comfort and/or safety. The increased VEP may also improve the therapeutic effects of the exogenous electrical signal.
Referring to FIG. 3D, a trace 306 illustrating the average potential inside the monkey thalamus observed over a series of 20 microbursts, each having a series of four pulses with a 3 milliseconds interpulse interval separating the pulses, is provided. The microbursts of FIG. 3D are separated by a 4 second inter-microburst interval. The VEP is the difference between a minimum 307 in the trace 306 observed after an averaged microburst portion 309 of the trace 306 and a maximum 308 in the trace 306
observed after the averaged microburst portion 309 of the trace 306. The difference between the minimum 307 and the maximum 308 of the trace 306 is clearly larger than the difference between the unidentifiable minimum and the unidentifiable maximum of the trace 320 (see FIG. 4A and the pulse intervals after the third pulse in FIG. 3B). Therefore, without changing any parameters other than the number of pulses delivered every 4 sec, i.e., delivering a microburst instead of a single pulse, the VEP potential can be increased or enhanced.
The pulses 402 and 404 within the first microburst 410A are separated by an interpulse interval "P1 A." The pulses 402 and 404 within the second microburst 41 OB are separated by an interpulse interval "P1 B." The pulses 402 and 404 within the third microburst 41 OC are separated by an interpulse interval "P1 C." In most cases, the interpulse intervals "P1 A," "P1 B,"and "P1 C" separating the pulses 402 and 404 are shorter than the interpulse intervals between the pulses 302 used in conventional VNS therapy. The first interpulse interval "P1 A" may range from about one millisecond to about 50 milliseconds. Typically, the first interpulse interval "P1 A" may range from about 2 milliseconds to about 10 milliseconds. In some embodiments, Typically, the first interpulse interval "P1 A" may range from about 3 milliseconds to about 10 milliseconds. In various embodiments, the interpulse interval "P1 B" may be substantially equal to the interpulse interval "P1 A." Subsequent interpulse intervals occurring after the interpulse interval "P1 B," such as interpulse interval "P1 C," may be substantially equal to the interpulse interval "P1 B." In alternate embodiments, the interpulse interval "P1 A" may be larger than the interpulse interval "P1 B," which may be larger than the interpulse interval "P1 C." In further embodiments, the interpulse interval "P1 A" may be smaller than the interpulse interval "P1 B," which may be smaller than the interpulse interval "P1 C." In various embodiments, the interpulse intervals "P1 A," "P1 B," and "P1 C" may be selected randomly from a predetermined range of interpulse interval values. In further embodiments, the interpulse intervals may be variable and determined empirically, as described below. The first microburst 41 OA is separated from the microburst 41 OB by an inter-microburst interval "P2." Each microburst may be considered an event occurring at a microburst frequency (i.e., the inverse of the sum of the inter-microburst interval "P2" and the duration of the microburst). The microburst frequency may range
from about 0.25 Hz to about 10 Hz. It may be beneficial to use a microburst frequency that approximates the R-R cycle of the patient.
In various embodiments, the pulses within a microburst may be patterned or structured. For example, referring to FIG. 1 , the portion of the pulse burst 130 is provided. The pulse burst 130 includes five microbursts 170, each triggered by the R- wave portion 176 of the cardiac cycle depicted in the ECG trace 120. Each microburst 170 includes four pulses 182, 184, 186, and 188. The first pulse 182 begins after the predetermined delay time "D1 " has elapsed following the identification of the R-wave portion 176. The pulse 184 follows the pulse 182 after a first interpulse delay has elapsed. Then, after a second interpulse interval, the pulse 186 is generated.
Finally, after a third interpulse interval, the pulse 188 is generated. In the embodiment depicted in FIG. 1 , the interpulse intervals increase in duration along the series of pulses. However, the interpulse intervals may be determined empirically and individualized for each patient. While each microburst 170 in FIG. 1 has only four pulses, microbursts 170 having 2 to 20 pulses, and consequently 1 to 19 interpulse intervals, are within the scope of the present invention. In some embodiments, the microbursts 170 may have 2 to 15 pulse, or alternatively, 3 to 6 pulses.
In various embodiments, the pulse burst 400 may be separated from a pulse burst identical to pulse burst 400 or a dissimilar pulse burst by an interburst interval of about 5 minutes to about 240 minutes. Alternatively, the interburst interval may be about 200 milliseconds to about 24 hours. In further embodiments, the pulse burst is applied continuously. The pulse burst may have a duration of about 100 milliseconds to about 60 minutes. In various embodiments, the pulse burst duration is determined empirically for a particular patient and/or medical condition. In further embodiments, the pulse burst 400 is triggered by the onset of a medical event, such as a seizure, or is triggered by the user or a medical professional. In such embodiments, the interburst interval varies. Optionally, the pulse burst 400 may be terminated automatically by the onset of a medical event, such as cardiac arrest, or manually the user or a medical professional. In such embodiments, the pulse burst duration varies. Pulses, such as pulses 182, 184, 186, and 188, arranged into microbursts, such as microburst 170, are capable of evoking an enhanced vagal evoked potential (eVEP) in the patient's brain that is significantly greater than an VEP evoked by conventional VNS (see FIG. 3A). However, this eVEP may attenuate as the number of pulses within a microburst increases beyond an optimal number of pulses.
Framed a little differently, the eVEP attenuates as the microburst duration increases beyond an optimal duration. Thus, for example, where a microburst exceeds 2 pulses to 5 pulses, the eVEP begins to diminish, and if more than 20 pulses are provided, the eVEP essentially disappears. This may be observed in FIG. 3E. Referring to the top row of FIG. 3E, traces 370, 372, and 374 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of 3 milliseconds. The microbursts of FIG. 3E are separated by a 4 second inter-microburst interval. The number of pulses within the microbursts increase from left to right. In the leftmost trace 370, the microbursts had 2 pulses each. In the center trace 372, the microbursts had 5 pulses each. And, in the rightmost trace 374, the microbursts had 9 pulses each. Again, the VEP observed in each trace, is the difference between a minimum in the trace observed after an averaged microburst portion (appearing at the left of the trace) and a maximum in the trace observed after the averaged microburst portion of the trace. The top row clearly illustrates that using these parameters, microbursts having 5 pulses produce a larger VEP than microbursts having 2 pulses. However, microbursts having 9 pulses produce a smaller VEP than microbursts having 5 pulses.
Referring to the middle row of FIG. 3E, traces 380, 382, and 384 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of 6 milliseconds. In the leftmost trace 380, the microbursts had 2 pulses each. In the center trace 382, the microbursts had 3 pulses each. And, in the rightmost trace 384, the microbursts had 6 pulses each. The middle row clearly illustrates that using these parameters, microbursts having 3 pulses produce a larger VEP than microbursts having 2 pulses. However, microbursts having 6 pulses produce a smaller VEP than microbursts having 3 pulses.
Referring to the bottom row of FIG. 3E, traces 390, 392, and 394 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of 9 milliseconds. In the leftmost trace 390, the microbursts had 2 pulses each. In the center trace 392, the microbursts had 3 pulses each. And, in the rightmost trace 394, the microbursts had 5 pulses each. The bottom row clearly illustrates that using these parameters, microbursts having 3 pulses produce a larger VEP than microbursts having
2 pulses. However, microbursts having 5 pulses produce a smaller VEP than microbursts having 3 pulses.
Referring to the leftmost column of FIG. 3E, traces 370, 380, and 390 illustrate the facilitation the first pulse provides to the second pulse of the microburst. The traces 372, 382, and 392 in the rightmost column of FIG. 3E illustrate additional facilitation provided by adding additional pulses to the microburst. However, the traces 374, 384, and 394 in the rightmost column of FIG. 3E illustrate that if the duration of the microbursts is too long, the microburst extends into an inhibitory period of neural activity reducing the VEP observed in the thalamus of the monkey. Consequently, the VEP may be improved and/or optimized by the selection of the number of pulses of the microbursts.
It may be helpful to define a microburst by its duration rather than the number of pulses. Experimental results related to optimizing microburst duration are illustrated in FIG. 3E and 4B. For example, ignoring the pulse widths, FIG. 3E illustrates that the VEP begins to decline when the sum of the interpulse intervals within a single microburst exceeds about 30 milliseconds. Consequently, for the monkey, the optimal sum of the interpulse intervals within a single microburst may be less than 30 milliseconds and in some embodiments, less than 20 milliseconds. The data of FIG. 3E further indicates, a range of about 12 milliseconds to about 18 milliseconds may be used. Human beings are larger and have a heart rate that is roughly half (about 180 beats/minute for the monkey and about 70 beats/minute for a human). Therefore, one of ordinary skill will recognize that by doubling the sum of the interpulse intervals, the sum of the interpulse intervals may be converted for use with a human. Based on this rough approximation, for humans, the optimal sum of the interpulse intervals within a single microburst may be less than 80 milliseconds and in some embodiments, the sum may be less than 60 milliseconds. In further embodiments, the sum of the interpulse intervals within a single microburst may be less than about 40 milliseconds and preferably about 12 milliseconds to about 40 milliseconds. In some embodiments, the sum of the interpulse intervals within a single microburst may be about 10 milliseconds to about 80 milliseconds. One of ordinary skill in the art will also recognize alternate methods of converting the sum of the interpulse intervals determined in the experimental monkey data for use with a human and that such embodiments are within the scope of the present invention. Further, the sum of the interpulse intervals for use
with a human may be determined empirically using the empirical method described below.
Generally, the microburst duration (i.e., the sum of the interpulse intervals and the pulse widths within a microburst) may be less than about one second. In particular embodiments, the microburst duration may be less than about 100 milliseconds. In particular embodiments, microbursts having a duration of about 4 milliseconds to about 40 milliseconds may be used.
Referring to the top row of FIG. 3F, traces 391 , 393, and 395 illustrate the average potential inside the monkey thalamus averaged over a series of 20 microbursts, each having a series of pulses separated by an interpulse interval of about 9 milliseconds. The microbursts used to create the traces 391 , 393, and 395 are separated by about a 6 second, about a 2 second, and about a 0.5 second inter- microburst interval, respectively. While the VEP in the trace 395 is less than the VEP in the other two traces 393, and 395, the trace 395 illustrates that the eVEP is present at the rate the QRS wave occurs in the cardiac cycle during inspiration, i.e., about once every 0.5 second. Consequently, microbursts synchronized with the QRS wave during inspiration may produce eVEP in the thalamus and other brain structures in electrical communication therewith. Other parameters, such as interpulse interval(s), delay period(s), pulse current amplitude, pulse width, pulse burst duration, and the like may be adjusted to improve and/or optimize the VEP.
To maintain the eVEP, the present invention provides a microburst having only a small number of pulses as well as an inter-microburst interval that serves as a period during which the vagus nerve (and/or brain structures in communication therewith) may recover from the microburst. Providing an appropriate inter-microburst interval helps ensure that the succeeding microburst in the pulse burst of the exogenous electrical signal is capable of generating the eVEP. In some embodiments, the inter-microburst interval is as long as or longer than the duration of the microburst. In another embodiment, the inter-microburst interval is at least 100 milliseconds. In further embodiments, the inter-microburst interval may be as long as 4 seconds or 6 seconds. In some embodiments, the inter-microburst interval may be as long as 10 seconds. Each microburst comprises a series of pulses that, in some embodiments, are intended to mimic the endogenous afferent activity on the vagus nerve. In one embodiment, the microburst may simulate the endogenous afferent vagal action, such as the action potentials associated with each cardiac and respiratory cycle.
The central vagal afferent pathways involve two or more synapses before producing activity in the forebrain. Each synaptic transfer is a potential site of facilitation and a nonlinear temporal filter, for which the sequence of inter-microburst intervals and/or interpulse intervals within a microburst can be optimized. Without being bound by theory, it is believed that the use of microbursts enhances VNS efficacy by augmenting synaptic facilitation and "tuning" the input stimulus train to maximize the forebrain evoked potential.
FIG. 4A-4C illustrate the effects of modifying the various parameters of the exogenous electrical signal on the VEP measured in the thalamus of a monkey. FIG. 4A illustrates the effects of varying the number of pulses in a microburst. FIG. 4B illustrates the effects of varying the interpulse interval between the pulses of a microburst having only two pulses. FIG. 4C illustrates the effects of varying the inter- microburst interval between adjacent microbursts having only two pulses each.
The topmost trace 320 of FIG. 4A provides the average potential (after 20 pulses) measured in the monkey thalamus while a pulse burst of uniformly spaced apart pulses having an interpulse interval of 4 seconds was applied to the vagus nerve. A trace 340 of FIG. 4A depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each was applied to the vagus nerve. The inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds. The VEP (i.e., the difference between the minimum and maximum potentials observed after each microburst) is noticeably improved in the trace 340 when compared with the VEP of the trace 320.
A trace 350 depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of three pulses each was applied to the vagus nerve. The inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds. The VEP is noticeably improved in the trace 350 when compared with the VEP of the trace 340.
A trace 360 depicts the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of four pulses each was applied to the vagus nerve. The inter-microburst interval was about 4 seconds and the interpulse interval was about 3 milliseconds. The VEP is noticeably improved in the trace 360 when compared with the VEP of the trace 350.
Referring to FIG. 4B, the effect of the interpulse interval on the VEP is illustrated. Traces 500, 510, 520, 530, and 540 depict the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each, separated by an inter-microburst interval of 4 sec. was applied to the vagus nerve. The interpulse intervals were about 40 milliseconds, about 20 milliseconds, about 10 milliseconds, about 6.7 milliseconds, and about 3 milliseconds for the traces 500, 510, 520, 530, and 540, respectively. The VEP is barely visible in the trace 500. The VEP is noticeably improved in the trace 510 when compared with the VEP of the trace 500. The VEP is noticeably improved in the trace 520 when compared with the VEP of the trace 510. The VEP is noticeably improved in the trace 530 when compared with the VEP of the trace 520. However, the VEP in the trace 540 is noticeably less than the VEP 534 of the trace 530.
Referring to FIG. 4C, the effect of the inter-microburst interval on the VEP is illustrated. Traces 600, 610, 620, 630, and 640 depict the average potential (after 20 microbursts) measured in the monkey thalamus while a pulse burst having microbursts of two pulses each, the pulses being separated by an interpulse interval of 6.7 milliseconds, was applied to the vagus nerve. The inter-microburst intervals corresponded to the microbursts occurring at a microburst frequency of about 10 Hz, about 3 Hz, about 1 Hz, about 0.3 Hz, and about 0.25 Hz for the traces 600, 610, 620, 630, and 640, respectively. The VEP is barely visible in the trace 600. Because the inter-microburst internal was sufficiently short, the trace 600 shows a second microburst artifact 606 to the right of the first microburst artifact 602. The VEP is noticeably improved in the trace 610 when compared with the VEP of the trace 600. The VEP is noticeably improved in the trace 620 when compared with the VEP of the trace 610. The VEP is noticeably improved in the trace 630 when compared with the VEP of the trace 620. However, the VEP in the trace 640 is noticeably less than the VEP in the trace 630.
As depicted in FIG. 4A-4C, the VEP is enormously enhanced (resulting in eVEP) and optimized by using a microburst of pulses (two or more, FIG. 4A) at appropriate interpulse intervals (in this case, 6.7 milliseconds was optimal for the first interpulse interval, shown in FIG. 4B) and at a inter-microburst interval (i.e., microburst frequency) that approximates the R-R cycle (i.e., the frequency at which the R wave portion appears in the ECG trace) of the monkey (in this case, about 0.3 Hz, as shown in FIG. 4C).
The experimental results depicted in FIG. 3D-3F and 4A-4C were obtained using a pulse burst including microbursts that were not synchronized with the cardiac cycle. In additional experiments, the effect of synchronizing the pulse bursts with the cardiac cycle was shown. Specifically, a single pulse was delivered at various times following every third R-wave. The VEP values obtained were then correlated with respiration. With respect to synchronization with the cardiac cycle, the experiments showed that the largest VEP was obtained when the pulse was delivered within 250 milliseconds after the initiation of a breath (which is accompanied by a decrease in the R-R interval). With respect to the delay period, the experiments showed that the greatest improvement in the VEP was obtained when the pulse was delivered about 400 milliseconds after the R-wave.
Additionally, the experimental data showed that by timing the pulse properly, an improvement in efficacy on the order of a factor of ten was obtained. Specifically, when the pulse was delivered about 0.5 seconds to about 1.0 second following the initiation of respiration and within 50 milliseconds following the R-wave, the VEP had a peak-to-peak amplitude of about 0.2 mV to about 0.4 mV. In contrast, when the pulse was delivered about 250 milliseconds after the initiation of inspiration and about 400 milliseconds following the R-wave, the VEP had a peak-to-peak amplitude of about 1.2 mV to about 1.4 mV. At maximum, this corresponds to about a seven-fold improvement in the VEP. These data show that by synchronizing the stimulation with respect to the cardiorespiratory cycles of the monkey, the efficacy of the stimulus pulse can be greatly improved over that of asynchronous stimulus delivery. These measurements were made in a monkey under deep anesthesia. Consequently, those of ordinary skill would expect an even greater effect in an awake human. The use of pairs of pulses is a standard physiological tool for producing central responses by stimulation of small-diameter afferent fibers. However, according to the present invention, a pulse burst including microbursts of pulses having an appropriate sequence of interpulse intervals enormously enhances the effect of VNS. By selecting the appropriate signal parameters (e.g., pulse width, pulse frequency, interpulse interval(s), microburst frequency, microburst duration, number of pulses in the microbursts, etc.), the exogenous electrical signal applied to the vagus nerve may comprise a series of microbursts that each provide an eVEP.
As illustrated in FIG. 4A and 3E, a microburst duration greater than about 10 milliseconds (corresponding to 4 pulses having an interpulse interval of about
3 milliseconds.) produces a maximal eVEP in the thalamus of the monkey and an interpulse interval of about 6 milliseconds to about 9 milliseconds produces maximal facilitation by the first pulse of the second pulse. Accordingly, a brief microburst of pulses with a total duration of about 10 milliseconds to about 20 milliseconds and having an initial interpulse interval of about 6 milliseconds to about 9 milliseconds and subsequent intervals of similar or longer duration may produce an optimal VEP. This is because such microbursts of pulses simulate the pattern of naturally occurring action potentials in the small-diameter afferent vagal fibers that elicit the central response that the present enhanced and optimized therapy is most interested in evoking (see below). Selection of an appropriate inter-microburst interval to separate one microburst from the next may be performed experimentally, although as previously noted, a period of at least 100 milliseconds (preferably at least 500 milliseconds, and more preferably at least one second) and at least equal to the microburst duration may be desirable.
The most effective sequence of interpulse intervals will vary with the patient's HRV (cardiac and respiratory timing) and also between individual patients, and thus, in some embodiments, the parameters of the exogenous electrical signal, such as the number of pulses in a microburst, the interpulse interval(s), the inter-microburst interval(s), the duration of the pulse burst, the delay period(s) between each QRS wave and a microburst, the current amplitude, the QRS waves of the cardiac cycle after which a microburst will be applied, the pulse width, and the like may be optimized for each patient. As a standard microburst sequence for initial usage, a microburst of 2 or 3 pulses having an interpulse interval of about 5 milliseconds to about 10 milliseconds may be used to approximate the short burst of endogenous post-cardiac activity.
The inter-microburst interval may be determined empirically by providing microbursts with a steadily decreasing inter-microburst interval until the eVEP begins to decline. In some embodiments, the interpulse interval varies between the pulses. For example, the interpulse interval may increase between each successive pulse in the microburst, simulating the pattern of a decelerating post-synaptic potential, as illustrated in FIG. 1. In alternative embodiments, the interpulse intervals may decrease between each successive pulse in the microburst, or may be randomly determined within a pre-selected range, e.g., about 5 milliseconds to about 10 milliseconds. Alternatively, the interpulse interval may remain constant between successive pulses in the microburst (i.e., providing a simple pulse train). Further, in a method described below, the interpulse intervals may be specified between each successive pair of
pulses using the VEP determined by an EEG. These modifications to the conventional VNS methodology produce a significant enhancement of VNS efficacy that is applicable to all VNS protocols and to many different medical conditions, including disorders of the nervous system. As noted above, the stimulation parameters (e.g., interpulse interval(s), inter-microburst interval(s), number of pulses per microburst, etc.) may be individually optimized for each patient. The optimization is accomplished by using surface electrodes to detect a far-field VEP, originating in the thalamus and other regions of the forebrain, and varying the stimulus parameters to maximize the VEP detected. As illustrated in FIG. 5, standard EEG recording equipment 700 and a 16-lead or a 25-lead electrode placement 710 of the EEG surface electrodes 712, such as that typically used clinically for recording somatosensory or auditory evoked potentials, enables the VEP present in the patient's forebrain to be detected, using VNS stimulus microburst timing to synchronize averages of about 8 epochs to about 12 epochs. The EEG recording equipment 700 may be used to produce continuous EEG waveforms 720 and recordings 730 thereof. By testing the effects of varying the parameters of the exogenous electrical signal, the VEP can be optimized for each patient.
The exogenous electrical signal used to deliver VNS is optimized in individual patients by selecting stimulus parameters that produce the greatest effect as measured by EEG surface electrodes 740. The pulse current amplitude and pulse width is first optimized by measuring the size of the VEP elicited by individual pulses (and not microbursts). The number of pulses, interpulse intervals, and inter-microburst intervals are then optimized (using the current amplitude and pulse width determined previously) by measuring the magnitude of the VEP evoked by the microbursts, as well as the effects on de-synchronization in the continuous EEG recordings. It may be desirable to determine the number of pulses first and then determine the interpulse intervals between those pulses. In alternate embodiments, it may be desirable to determine the number of pulses first, followed by the microburst duration, and lastly, the interpulse intervals between the pulses. Because the large eVEPs recorded in the thalamus, striatum, and insular cortex of the anesthetized monkey and shown in FIG. 4A-4C, are large enough that if evoked in a human patient, the eVEPs are observable in a standard EEG detected using electrodes adjacent to the human patient's scalp, the standard EEG may be used to indicate the effects of modifications to the signal parameters of the exogenous
electrical signal. In this manner, the EEG may be used to optimize or tune the signal parameters of the exogenous electrical signal empirically. For a human patient, this method provides a safe and non-invasive way to customize the various signal parameters for the patient and/or the treatment of the patient's medical condition. The eVEP recorded in the right thalamus and right striatum is significant for the anti-epileptic effects of VNS, whereas the eVEP recorded in the left insular cortex is most significant for the anti-depression effects of VNS. By using regional EEG localization on the right or left frontal electrodes, the signal parameters of the exogenous electrical signal may be optimized appropriately to achieve an eVEP in the appropriate region of the individual patient's brain. Further, the magnitude of the measured VEP may be appropriately tuned for the patient.
The optimal exogenous electrical signal parameters for eliciting eVEPs from these two areas (right thalamus/striatum and left insular cortex, respectively) may differ. Both eVEPs are identifiable using known EEG recording methods in awake human patients. Therefore, EEG recordings made using these methods may be used to evaluate the eVEP in the appropriate area. The EEG recording may be used to collect samples of the eVEP in the appropriate area(s) and those samples may be used easily for a parametric optimization, in a patient suffering from a disorder of the nervous system such as epilepsy or depression. Similarly, the exogenous electrical signal parameters used for HRV-synchronization may be selected based on their effects on the VEP and on the heartbeat-related evoked potential both of which may be measured using known noninvasive EEG recording methods that use EEG electrodes attached to the patient's scalp.
Referring to FIG. 6, an exemplary EEG is provided. A pair of traces 810 and 812 correspond to the potential present in the left striatum and left insular cortex and a pair of traces 820 and 822 correspond to the potential present in the left striatum and left insular cortex. While the same traces 810, 812, 820 and 822 depict the potential present in striatum and insular cortex, the potential in the striatum may be distinguished from the potential in the insular cortex by its timing. Experiments have shown that pulses applied to the vagus nerve reach the parafascicular nucleus in the thalamus in about 18 milliseconds and the basal portion of the ventral medial nucleus in about 34 milliseconds. The parafascicular nucleus then projects the stimulus to the striatum and the basal portion of the ventral medial nucleus projects the stimulus to the insular cortex. Consequently, the potential evoked by the pulse burst in the striatum will
appear in the traces 810, 812, 820 and 822 before the potential evoked in the insular cortex. By analyzing the traces 810, 812, 820 and 822, the potential inside the striatum and/or the insular cortex may be observed and the signal parameter used to generate those potentials modified to enhance and/or optimize those potentials. In FIG. 6, the strong VEP shown in traces 820 and 822 corresponding to the right thalamus and the right striatum (or basal ganglia) is associated with the anti- epileptic effects of VNS. As mentioned above, distinguishing the right thalamus from the right insular cortex may be accomplished by analyzing the timing of the eVEP observed in the traces 820 and 822. The strong VEP shown in traces 810 and 812 corresponding to the left thalamus and left insular cortex is associated with the anti- depression effects of VNS. Traces 830 and 832 in the central portion of the EEG depict a weak VEP in the thalamus. Because the EEG method described is non-invasive, it offers a safe and effective method of enhancing and/or optimizing the therapeutic effects of the exogenous electrical signal. FIG. 7 illustrates one method of variable programming of the electrical signal generator 200 to optimize the eVEP in the right thalamus and striatum for epileptic patients, and in the left insula for patients suffering from depression. As shown in FIG. 7, a computer 900 may be coupled to and used to program the computer-controlled programming wand 800. The programming wand 800 may use radio frequency telemetry to communicate with the electrical signal generator 200 and program the burst duration, number of pulses in a microburst, interpulse interval(s), pulse frequency, microburst duration, inter-microburst interval, pulse width, and current amplitude of the exogenous electrical signal delivered by the electrical signal generator 200 to the vagus nerve of the patient. Using the programming wand 800, programming may be performed periodically or as needed on an implanted electrical signal generator 200. This provides the ability to continually optimize and change the exogenous electrical signal delivered by the electrical signal generator 200 depending on the EEG, and to respond to changes therein. Therefore, the present method of using one or more of the above referenced techniques, alone or in combination, significantly enhances and/or optimizes currently available VNS therapies.
Various embodiments of the invention are described above in the Detailed Description. While these descriptions directly describe the above embodiments, it is understood that those skilled in the art may conceive modifications and/or variations to the specific embodiments shown and described herein. Any such modifications or
variations that fall within the purview of this description are intended to be included therein as well. Unless specifically noted, it is the intention of the inventors that the words and phrases in the specification and claims be given the ordinary and accustomed meanings to those of ordinary skill in the applicable art(s). The foregoing description of various embodiments of the invention known to the applicant at this time of filing the application has been presented and is intended for the purposes of illustration and description. The present description is not intended to be exhaustive nor limit the invention to the precise form disclosed and many modifications and variations are possible in the light of the above teachings. The embodiments described serve to explain the principles of the invention and its practical application and to enable others skilled in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. Therefore, it is intended that the invention not be limited to the particular embodiments disclosed for carrying out the invention. While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from this invention and its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this invention. Furthermore, it is to be understood that the invention is solely defined by the appended claims. It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particular claim containing such introduced claim recitation to inventions containing only one such recitation, even when the same claim includes the introductory phrases "one
or more" or "at least one" and indefinite articles such as "a" or "an" (e.g., "a" and/or "an" should typically be interpreted to mean "at least one" or "one or more"); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of "two recitations," without other modifiers, typically means at least two recitations, or two or more recitations).
Accordingly, the invention is not limited except as by the appended claims.
Claims
1. A method of treating a medical condition in a patient having a vagus nerve and a heart that generates a cardiac signal having a QRS wave portion, comprising: detecting a portion of the QRS wave portion of the patient's cardiac signal; after detecting the portion of the QRS wave portion, generating a microburst comprising 2 to 20 electrical pulses; and delivering the microburst to the vagus nerve of the patient.
2. The method of claim 1 , further comprising, generating additional electrical pulses after detecting another QRS wave portion of the cardiac signal.
3. The method of claim 1 , further comprising, after detecting the portion of the QRS wave portion, waiting a predetermined delay period before generating the microburst.
4. The method of claim 1 , further comprising, after detecting the portion of the QRS wave portion, waiting less than about 1000 milliseconds before generating a second microburst comprising from 2 to 20 electrical pulses.
5. The method of claim 1 , wherein the electrical pulses of the microburst are generated in a series having a first pulse and a last pulse, each pulse other than the last pulse being separated from a successor pulse in the series by an interpulse interval having a duration, the duration of the interpulse interval increasing along the series from the first pulse to the last pulse.
6. The method of claim 1 , wherein the electrical pulses have a pulse width of from about 50 microseconds to about 1000 microseconds, and have a pulse current amplitude of from about 0.25 mA to about 8 mA.
7. The method of claim 1 , wherein the electrical pulses of the microburst are generated in a series having a last pulse, each pulse other than the last pulse of the series being separated from a successor pulse in the series by an interpulse interval, each interpulse interval being less than about 40 milliseconds.
8. The method of claim 1 , wherein the electrical pulses of the microburst are generated in a series having a last pulse, each pulse other than the last pulse of the series being separated from a successor pulse in the series by an interpulse interval, each interpulse interval having been determined empirically for the patient.
9. The method of claim 1 , wherein the electrical pulses of the microburst are generated in a series having a last pulse, each pulse other than the last pulse of the series being separated from a successor pulse in the series by an interpulse interval of about 3 milliseconds to about 10 milliseconds.
10. The method of claim 1 , wherein the patient is breathing and has a heart with a heart rate variability, the method further comprising restricting the patient's breathing to increase the heart rate variability.
1 1. An exogenous electrical signal adapted to be delivered to a vagus nerve of a patient having a brain and a medical condition, the vagus nerve evoking a vagal evoked potential in the brain, the exogenous electrical signal comprising a series of microbursts, each microburst in the series comprising from 2 to 20 electrical pulses, wherein the exogenous electrical signal is adapted to treat the medical condition by enhancing the vagal evoked potential in the brain.
12. An implantable device configured to apply the signal of claim 1 1.
13. An exogenous electrical signal adapted to be delivered to a vagus nerve of a patient having a brain and a medical condition, the vagus nerve evoking a vagal evoked potential in the brain, the exogenous electrical signal comprising a series of microbursts, each microburst having a duration less than about one second, wherein the exogenous electrical signal is adapted to treat the medical condition by enhancing the vagal evoked potential in the brain.
14. An implantable device configured to apply the signal of claim 13.
15. An exogenous electrical signal adapted to be delivered to a vagus nerve of a patient having a brain, a medical condition, and a heart operating in a cardiac cycle with an R wave portion, the vagus nerve evoking a vagal evoked potential in the brain, the exogenous electrical signal adapted to treat the medical condition by enhancing the vagal evoked potential in the brain, the signal comprising: a series of microbursts, each microburst comprising 2 to 20 electrical pulses, and each of the microbursts occurring after a selected R wave portion of the cardiac cycle.
16. The signal of claim 15, wherein each R wave portion is separated from a successive R wave portion by an R-R interval, each R-R interval has a duration and a previous R-R interval preceding it, and each of the microbursts occurs after an R- R interval having a duration that is shorter than the duration of the previous R-R interval.
17. The signal of claim 15, wherein the pulses of the microbursts are spaced to simulate endogenous afferent activity occurring at a particular time in the cardiac cycle.
18. The signal of claim 15, wherein each of the microbursts is delayed relative to the selected R wave portion to simulate endogenous afferent activity occurring at a particular time in the cardiac cycle.
19. The signal of claim 15, wherein each of the microbursts occurs less than about 1000 milliseconds after the selected R wave portion.
20. An exogenous electrical signal adapted to be delivered to a vagus nerve of a patient having a brain, lungs, a medical condition, and a heart with a cardiac signal comprising an inspiration portion corresponding to an inspiration of air by the lungs and an expiration portion corresponding to an expiration of air by the lungs, the inspiration portion having a series of R wave portions, the expiration portion having a series of R wave portions, the vagus nerve evoking a vagal evoked potential in the brain, the exogenous electrical signal adapted to be delivered to the vagus nerve to treat the condition or disorder of the nervous system by enhancing the vagal evoked potential in the brain, the signal comprising: a series of microbursts, each microburst in the series comprising from 2 to 20 electrical pulses, each of the microbursts being delivered to the vagus nerve in response to a selected R wave portion of the inspiration portion of the cardiac signal, and none of the microbursts being delivered in response to the R wave portions of the expiration portion of the cardiac signal.
21. The signal of claim 20, wherein the pulses of the microbursts are spaced to simulate endogenous afferent activity occurring at a particular time in the cardiac signal.
22. The signal of claim 20, wherein the pulses of the microbursts are spaced to simulate endogenous afferent activity occurring at a particular time during inspiration of air by the lungs.
23. The signal of claim 20, wherein the microbursts are spaced to simulate endogenous afferent activity occurring at a particular time in the cardiac signal.
24. The signal of claim 20, wherein the microbursts are spaced to simulate endogenous afferent activity occurring at a particular time during inspiration of air by the lungs.
25. A method of customizing an exogenous electrical signal adapted to be delivered to a vagus nerve of a patient having a brain and a medical condition, and to elicit a desired vagal evoked potential in a selected structure of the brain associated with the medical condition, the method comprising: determining a value of a signal parameter; generating an electrical signal according to the signal parameter, the electrical signal comprising a series of microbursts, each microburst comprising a series of from 2 to 20 electrical pulses; delivering the electrical signal to the vagus nerve of the patient; analyzing an EEG of the patient's brain created during the delivery of the electrical signal to the vagus nerve of the patient to determine the vagal evoked potential observed in the selected structure of the brain; and modifying the value of the signal parameter based on the vagal evoked potential observed in the selected structure of the brain to modify the vagal evoked potential observed therein.
26. The method of claim 25, wherein the selected structure of the brain includes a region selected from the group consisting of the thalamus, the striatum, the insular cortex, and combinations thereof.
27. The method of claim 25, wherein the signal parameter is a parameter selected from the group consisting of a pulse width, a pulse frequency, an interpulse interval between two of the pulses of the microburst, a frequency of the microbursts, a number of microbursts of the series of microburst, a duration of the electrical signal, a number of pulses in the microbursts, and combinations thereof.
28. The method of claim 25, wherein the patient has a heart that generates a series of QRS waves, each of the microbursts is delivered to the vagus nerve after a selected QRS wave of the series of QRS waves, and the signal parameter comprises a delay period between each microburst and the selected QRS wave.
29. The method of claim 25, wherein the patient has a heart that generates a series of QRS waves, and the signal parameter comprises a selected QRS wave of the series of QRS waves to precede each microburst of the series of microbursts.
30. A method of treating a medical condition in a patient having a vagus nerve and a heart that generates a cardiac signal having a QRS wave portion, comprising: detecting the QRS wave portion of the cardiac signal; generating a microburst comprising a series electrical pulses separated by an interpulse interval, the sum of the interpulse intervals separating the pulses being less than 60 milliseconds; and delivering the microburst to the vagus nerve of the patient.
31. The method of claim 30, further comprising, after detecting the QRS wave portion, waiting a predetermined delay period before applying the microburst to the vagus nerve.
32. The method of claim 30, further comprising, after detecting the QRS wave portion, waiting less than about 500 milliseconds before applying the microburst to the vagus nerve.
33. The method of claim 30, wherein the electrical pulses have a pulse width of from about 50 microseconds to about 1000 microseconds.
34. The method of claim 30, wherein the electrical pulses of the microburst are generated in a series having a last pulse, each pulse other than the last pulse of the series being separated from a successor pulse in the series by an interpulse interval, each interpulse interval being less than about 40 milliseconds.
35. The method of claim 30, wherein each of the interpulse intervals is determined empirically for the patient.
36. The method of claim 30, wherein each of the interpulse intervals is about 3 milliseconds to about 12 milliseconds.
37. The method of claim 30, wherein the patient is breathing and has a heart with a heart rate variability, the method further comprising restricting the patient's breathing to increase the heart rate variability.
38. A system for treating a medical condition in a patient having a vagus nerve and a heart that generates a cardiac signal having a QRS wave portion, the system comprising: a sensor configured to detect a portion of the QRS wave portion of the cardiac signal; an electrical signal generator configured to generate a microburst after the detection of the portion of the QRS wave portion by the sensor, the microburst having a duration of less than about one second; and an electrode in electrical communication with the vagus nerve, the electrode being configured to deliver the microburst to the vagus nerve of the patient.
39. The system of claim 38, wherein the duration of the microburst is less than about 100 milliseconds.
40. The system of claim 38, wherein the electrical signal generator is configured to wait a predetermined delay period after detection of the portion of the QRS wave portion wave before applying the microburst.
41. The system of claim 38, wherein the microburst comprises a series of electrical pulses having a last pulse, each pulse other than the last pulse of the series being separated from a successor pulse in the series by an interpulse interval of about 3 milliseconds to about 10 milliseconds.
42. A computer readable medium having computer executable components for detecting a QRS wave portion of a cardiac cycle; generating a microburst having 2 to 20 electrical pulses; and delivering the microburst via an electrode to the vagus nerve of a patient in response to the detection of the QRS wave portion of a cardiac cycle.
43. The computer readable medium of claim 42, wherein the electrical pulses of the microburst are generated in a series having a last pulse, each pulse other than the last pulse being separated from a successor pulse in the series by an interpulse interval having a duration, the computer readable medium further comprising computer executable components for determining the duration of each of the interpulse intervals.
44. A method of treating a medical condition in a patient having a vagus nerve, comprising allowing the patient to manually trigger generation of an exogenous electrical signal comprising a microburst having a duration of less than about one second; and delivering the exogenous electrical signal to the vagus nerve of the patient.
45. The method of claim 45, wherein the patient has a heart that generates a cardiac signal having a QRS wave portion, the method further comprising, detecting the QRS wave portion of the cardiac signal and delivering the microburst of the exogenous electrical signal to the vagus nerve of the patient in response to detection of the QRS wave portion.
46. The method of claim 45, wherein the patient is performing paced breathing before triggering the exogenous electrical signal.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES07759728.4T ES2538726T3 (en) | 2006-03-29 | 2007-03-29 | Vagus nerve stimulation system |
EP20070759728 EP2026874B1 (en) | 2006-03-29 | 2007-03-29 | Vagus nerve stimulation system |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US78768006P | 2006-03-29 | 2006-03-29 | |
US60/787,680 | 2006-03-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007115118A1 true WO2007115118A1 (en) | 2007-10-11 |
Family
ID=38268962
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2007/065518 WO2007115103A1 (en) | 2006-03-29 | 2007-03-29 | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
PCT/US2007/065537 WO2007115118A1 (en) | 2006-03-29 | 2007-03-29 | Vagus nerve stimulation method |
PCT/US2007/065531 WO2007115113A1 (en) | 2006-03-29 | 2007-03-29 | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2007/065518 WO2007115103A1 (en) | 2006-03-29 | 2007-03-29 | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2007/065531 WO2007115113A1 (en) | 2006-03-29 | 2007-03-29 | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
Country Status (9)
Country | Link |
---|---|
US (15) | US8150508B2 (en) |
EP (7) | EP2965781B1 (en) |
JP (3) | JP5052596B2 (en) |
AU (2) | AU2007233135B2 (en) |
BR (2) | BRPI0709844A2 (en) |
CA (3) | CA2653110C (en) |
ES (3) | ES2566730T3 (en) |
IL (2) | IL194407A (en) |
WO (3) | WO2007115103A1 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010047760A1 (en) * | 2008-10-20 | 2010-04-29 | Cyberonics, Inc. | Neurostimulation with signal duration determined by a cardiac cycle |
US9108041B2 (en) | 2006-03-29 | 2015-08-18 | Dignity Health | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
CN108126274A (en) * | 2014-12-21 | 2018-06-08 | 徐志强 | The multi-channel nerve stimulating apparatus of impulse stimulation is carried out to depth stupor brain |
EP3793671A4 (en) * | 2018-05-15 | 2022-02-23 | Livanova USA, Inc. | Display signal to asses autonomic response to vagus nerve stimulation treatment |
EP3793668A4 (en) * | 2018-05-15 | 2022-03-02 | Livanova USA, Inc. | Poincare display to assess autonomic engagement responsive to vagus nerve stimulation |
EP3793669A4 (en) * | 2018-05-15 | 2022-03-02 | Livanova USA, Inc. | R-r interval analysis for ecg waveforms to assess autonomic response to vagus nerve simulation |
US11786740B2 (en) | 2018-05-15 | 2023-10-17 | Livanova Usa, Inc. | Assessment system with wand detection cable synchronizing ECG recording |
Families Citing this family (230)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7444183B2 (en) | 2003-02-03 | 2008-10-28 | Enteromedics, Inc. | Intraluminal electrode apparatus and method |
US9050469B1 (en) | 2003-11-26 | 2015-06-09 | Flint Hills Scientific, Llc | Method and system for logging quantitative seizure information and assessing efficacy of therapy using cardiac signals |
US10912712B2 (en) | 2004-03-25 | 2021-02-09 | The Feinstein Institutes For Medical Research | Treatment of bleeding by non-invasive stimulation |
CN101128149B (en) * | 2004-12-13 | 2010-05-12 | 卡迪科尔实验室公司 | Transfer of captured electrocardiogram |
US11207518B2 (en) * | 2004-12-27 | 2021-12-28 | The Feinstein Institutes For Medical Research | Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway |
US8260426B2 (en) | 2008-01-25 | 2012-09-04 | Cyberonics, Inc. | Method, apparatus and system for bipolar charge utilization during stimulation by an implantable medical device |
US9314633B2 (en) | 2008-01-25 | 2016-04-19 | Cyberonics, Inc. | Contingent cardio-protection for epilepsy patients |
US8565867B2 (en) | 2005-01-28 | 2013-10-22 | Cyberonics, Inc. | Changeable electrode polarity stimulation by an implantable medical device |
WO2007013065A2 (en) | 2005-07-25 | 2007-02-01 | Rainbow Medical Ltd. | Electrical stimulation of blood vessels |
US9037247B2 (en) | 2005-11-10 | 2015-05-19 | ElectroCore, LLC | Non-invasive treatment of bronchial constriction |
US9174066B2 (en) * | 2009-03-20 | 2015-11-03 | ElectroCore, LLC | Devices and methods for non-invasive capacitive electrical stimulation and their use for vagus nerve stimulation on the neck of a patient |
US7996079B2 (en) | 2006-01-24 | 2011-08-09 | Cyberonics, Inc. | Input response override for an implantable medical device |
US7869885B2 (en) | 2006-04-28 | 2011-01-11 | Cyberonics, Inc | Threshold optimization for tissue stimulation therapy |
US7962220B2 (en) | 2006-04-28 | 2011-06-14 | Cyberonics, Inc. | Compensation reduction in tissue stimulation therapy |
US7869867B2 (en) | 2006-10-27 | 2011-01-11 | Cyberonics, Inc. | Implantable neurostimulator with refractory stimulation |
US8615296B2 (en) | 2007-03-06 | 2013-12-24 | Cardiac Pacemakers, Inc. | Method and apparatus for closed-loop intermittent cardiac stress augmentation pacing |
US7904175B2 (en) | 2007-04-26 | 2011-03-08 | Cyberonics, Inc. | Trans-esophageal vagus nerve stimulation |
US7962214B2 (en) | 2007-04-26 | 2011-06-14 | Cyberonics, Inc. | Non-surgical device and methods for trans-esophageal vagus nerve stimulation |
US7869884B2 (en) | 2007-04-26 | 2011-01-11 | Cyberonics, Inc. | Non-surgical device and methods for trans-esophageal vagus nerve stimulation |
US7974701B2 (en) * | 2007-04-27 | 2011-07-05 | Cyberonics, Inc. | Dosing limitation for an implantable medical device |
WO2009029614A1 (en) * | 2007-08-27 | 2009-03-05 | The Feinstein Institute For Medical Research | Devices and methods for inhibiting granulocyte activation by neural stimulation |
US8571643B2 (en) | 2010-09-16 | 2013-10-29 | Flint Hills Scientific, Llc | Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex |
US8337404B2 (en) | 2010-10-01 | 2012-12-25 | Flint Hills Scientific, Llc | Detecting, quantifying, and/or classifying seizures using multimodal data |
US8382667B2 (en) | 2010-10-01 | 2013-02-26 | Flint Hills Scientific, Llc | Detecting, quantifying, and/or classifying seizures using multimodal data |
US9005106B2 (en) | 2008-01-31 | 2015-04-14 | Enopace Biomedical Ltd | Intra-aortic electrical counterpulsation |
US8538535B2 (en) | 2010-08-05 | 2013-09-17 | Rainbow Medical Ltd. | Enhancing perfusion by contraction |
WO2009102969A1 (en) * | 2008-02-14 | 2009-08-20 | Enteromedics, Inc. | Treatment of excess weight by neural downregulation in combination with compositions |
US9662490B2 (en) | 2008-03-31 | 2017-05-30 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation and administration of an anti-inflammatory drug |
WO2009146030A1 (en) * | 2008-03-31 | 2009-12-03 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation of t-cell activity |
US8204603B2 (en) | 2008-04-25 | 2012-06-19 | Cyberonics, Inc. | Blocking exogenous action potentials by an implantable medical device |
US8473062B2 (en) | 2008-05-01 | 2013-06-25 | Autonomic Technologies, Inc. | Method and device for the treatment of headache |
US8788042B2 (en) | 2008-07-30 | 2014-07-22 | Ecole Polytechnique Federale De Lausanne (Epfl) | Apparatus and method for optimized stimulation of a neurological target |
WO2010035600A1 (en) * | 2008-09-25 | 2010-04-01 | テルモ株式会社 | Pain relief device |
GB2476918A (en) * | 2008-10-20 | 2011-07-13 | Seaboard Assets Corp | Cranial electrostimulation device for treatment of polysusbstance addiction and method of use |
US8417344B2 (en) | 2008-10-24 | 2013-04-09 | Cyberonics, Inc. | Dynamic cranial nerve stimulation based on brain state determination from cardiac data |
JP2010099415A (en) * | 2008-10-27 | 2010-05-06 | Olympus Corp | Heart treatment apparatus |
US8255057B2 (en) | 2009-01-29 | 2012-08-28 | Nevro Corporation | Systems and methods for producing asynchronous neural responses to treat pain and/or other patient conditions |
CA2743575C (en) | 2008-11-12 | 2017-01-31 | Ecole Polytechnique Federale De Lausanne | Microfabricated neurostimulation device |
WO2010059617A2 (en) | 2008-11-18 | 2010-05-27 | Setpoint Medical Corporation | Devices and methods for optimizing electrode placement for anti-inflamatory stimulation |
US8412336B2 (en) | 2008-12-29 | 2013-04-02 | Autonomic Technologies, Inc. | Integrated delivery and visualization tool for a neuromodulation system |
US8494641B2 (en) | 2009-04-22 | 2013-07-23 | Autonomic Technologies, Inc. | Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism |
US9320908B2 (en) | 2009-01-15 | 2016-04-26 | Autonomic Technologies, Inc. | Approval per use implanted neurostimulator |
US20100191304A1 (en) | 2009-01-23 | 2010-07-29 | Scott Timothy L | Implantable Medical Device for Providing Chronic Condition Therapy and Acute Condition Therapy Using Vagus Nerve Stimulation |
EP3228350A1 (en) * | 2009-04-22 | 2017-10-11 | Nevro Corporation | Selective high frequency spinal cord modulation for inhibiting pain with reduced side effects, and associated systems and methods |
US8239028B2 (en) | 2009-04-24 | 2012-08-07 | Cyberonics, Inc. | Use of cardiac parameters in methods and systems for treating a chronic medical condition |
US8827912B2 (en) | 2009-04-24 | 2014-09-09 | Cyberonics, Inc. | Methods and systems for detecting epileptic events using NNXX, optionally with nonlinear analysis parameters |
US8886339B2 (en) | 2009-06-09 | 2014-11-11 | Setpoint Medical Corporation | Nerve cuff with pocket for leadless stimulator |
US8996116B2 (en) * | 2009-10-30 | 2015-03-31 | Setpoint Medical Corporation | Modulation of the cholinergic anti-inflammatory pathway to treat pain or addiction |
US9211410B2 (en) | 2009-05-01 | 2015-12-15 | Setpoint Medical Corporation | Extremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
US8958873B2 (en) * | 2009-05-28 | 2015-02-17 | Cardiac Pacemakers, Inc. | Method and apparatus for safe and efficient delivery of cardiac stress augmentation pacing |
US9399132B2 (en) | 2009-06-30 | 2016-07-26 | Boston Scientific Neuromodulation Corporation | Method and device for acquiring physiological data during tissue stimulation procedure |
US9566439B2 (en) * | 2009-07-20 | 2017-02-14 | Saluda Medical Pty Limited | Neuro-stimulation |
US8812104B2 (en) | 2009-09-23 | 2014-08-19 | Cardiac Pacemakers, Inc. | Method and apparatus for automated control of pacing post-conditioning |
BR112012008029A2 (en) | 2009-10-05 | 2016-03-01 | Univ California | trigeminal nerve stimulation system for treating a neurological disorder or condition, skin electrode unit, method for treating a neurological disorder or condition, and trigeminal nerve stimulation kit for treating a neurological disorder or condition |
EP2485801B1 (en) * | 2009-10-12 | 2018-05-02 | NewSouth Innovations Pty Limited | Method of power and data transfer in implantable electronic devices |
JP2011103981A (en) * | 2009-11-13 | 2011-06-02 | Olympus Corp | Nerve stimulation device |
WO2014169145A1 (en) | 2013-04-10 | 2014-10-16 | Setpoint Medical Corporation | Closed-loop vagus nerve stimulation |
US9833621B2 (en) | 2011-09-23 | 2017-12-05 | Setpoint Medical Corporation | Modulation of sirtuins by vagus nerve stimulation |
JP2013512062A (en) | 2009-12-01 | 2013-04-11 | エコーレ ポリテクニーク フェデラーレ デ ローザンヌ | Microfabricated surface nerve stimulation device and methods of making and using the same |
AU2010336337B2 (en) | 2009-12-23 | 2016-02-04 | Setpoint Medical Corporation | Neural stimulation devices and systems for treatment of chronic inflammation |
US9002472B2 (en) * | 2010-02-26 | 2015-04-07 | Intelect Medical, Inc. | Neuromodulation having non-linear dynamics |
US8818508B2 (en) * | 2010-03-12 | 2014-08-26 | Medtronic, Inc. | Dosing vagal nerve stimulation therapy in synchronization with transient effects |
WO2011121089A1 (en) | 2010-04-01 | 2011-10-06 | Ecole Polytechnique Federale De Lausanne (Epfl) | Device for interacting with neurological tissue and methods of making and using the same |
AU2011239668B2 (en) | 2010-04-15 | 2014-04-17 | Cardiac Pacemakers, Inc. | Autonomic modulation using transient response with intermittent neural stimulation |
US8562536B2 (en) | 2010-04-29 | 2013-10-22 | Flint Hills Scientific, Llc | Algorithm for detecting a seizure from cardiac data |
US8831732B2 (en) | 2010-04-29 | 2014-09-09 | Cyberonics, Inc. | Method, apparatus and system for validating and quantifying cardiac beat data quality |
US8649871B2 (en) | 2010-04-29 | 2014-02-11 | Cyberonics, Inc. | Validity test adaptive constraint modification for cardiac data used for detection of state changes |
US20110282225A1 (en) * | 2010-05-12 | 2011-11-17 | Medtronic, Inc. | Techniques for reviewing and analyzing implantable medical device system data |
AU2015202725B2 (en) * | 2010-06-11 | 2017-06-08 | Reshape Lifesciences, Inc. | Neural modulation devices and methods |
US8825164B2 (en) | 2010-06-11 | 2014-09-02 | Enteromedics Inc. | Neural modulation devices and methods |
US8679009B2 (en) | 2010-06-15 | 2014-03-25 | Flint Hills Scientific, Llc | Systems approach to comorbidity assessment |
US8641646B2 (en) | 2010-07-30 | 2014-02-04 | Cyberonics, Inc. | Seizure detection using coordinate data |
US8684921B2 (en) | 2010-10-01 | 2014-04-01 | Flint Hills Scientific Llc | Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis |
US8562523B2 (en) | 2011-03-04 | 2013-10-22 | Flint Hills Scientific, Llc | Detecting, assessing and managing extreme epileptic events |
US8562524B2 (en) | 2011-03-04 | 2013-10-22 | Flint Hills Scientific, Llc | Detecting, assessing and managing a risk of death in epilepsy |
KR20120036244A (en) * | 2010-10-07 | 2012-04-17 | 삼성전자주식회사 | Implantable medical device(imd) and method for controlling of the imd |
WO2012075192A2 (en) | 2010-11-30 | 2012-06-07 | The Regents Of The University Of California | Pulse generator for cranial nerve stimulation |
EP2651496A4 (en) | 2010-12-14 | 2014-07-09 | Univ California | Devices, systems and methods for the treatment of medical disorders |
JP6559395B2 (en) | 2010-12-14 | 2019-08-14 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Extracranial implantable system for the treatment of medical disorders |
US11432760B2 (en) * | 2011-01-12 | 2022-09-06 | Electrocore, Inc. | Devices and methods for remote therapy and patient monitoring |
US9504390B2 (en) | 2011-03-04 | 2016-11-29 | Globalfoundries Inc. | Detecting, assessing and managing a risk of death in epilepsy |
US8725239B2 (en) | 2011-04-25 | 2014-05-13 | Cyberonics, Inc. | Identifying seizures using heart rate decrease |
US9789307B2 (en) | 2011-04-29 | 2017-10-17 | Medtronic, Inc. | Dual prophylactic and abortive electrical stimulation |
US9402550B2 (en) | 2011-04-29 | 2016-08-02 | Cybertronics, Inc. | Dynamic heart rate threshold for neurological event detection |
US10448889B2 (en) | 2011-04-29 | 2019-10-22 | Medtronic, Inc. | Determining nerve location relative to electrodes |
US9649494B2 (en) | 2011-04-29 | 2017-05-16 | Medtronic, Inc. | Electrical stimulation therapy based on head position |
WO2012154865A2 (en) | 2011-05-09 | 2012-11-15 | Setpoint Medical Corporation | Single-pulse activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
JP5881326B2 (en) | 2011-07-08 | 2016-03-09 | オリンパス株式会社 | Nerve stimulation device, nerve stimulation system, and method for controlling nerve stimulation device |
US9566426B2 (en) * | 2011-08-31 | 2017-02-14 | ElectroCore, LLC | Systems and methods for vagal nerve stimulation |
WO2013035092A2 (en) | 2011-09-09 | 2013-03-14 | Enopace Biomedical Ltd. | Wireless endovascular stent-based electrodes |
JP5846816B2 (en) * | 2011-09-15 | 2016-01-20 | オリンパス株式会社 | Nerve stimulator |
US10206591B2 (en) | 2011-10-14 | 2019-02-19 | Flint Hills Scientific, Llc | Seizure detection methods, apparatus, and systems using an autoregression algorithm |
US8577458B1 (en) * | 2011-12-07 | 2013-11-05 | Cyberonics, Inc. | Implantable device for providing electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction with leadless heart rate monitoring |
US10188856B1 (en) | 2011-12-07 | 2019-01-29 | Cyberonics, Inc. | Implantable device for providing electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction |
US8918190B2 (en) * | 2011-12-07 | 2014-12-23 | Cyberonics, Inc. | Implantable device for evaluating autonomic cardiovascular drive in a patient suffering from chronic cardiac dysfunction |
US8600505B2 (en) * | 2011-12-07 | 2013-12-03 | Cyberonics, Inc. | Implantable device for facilitating control of electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction |
US9345885B2 (en) * | 2011-12-07 | 2016-05-24 | Med-El Elektromedizinische Geraete Gmbh | Pacemaker for unilateral vocal cord autoparalysis |
CN103998096B (en) | 2011-12-07 | 2016-06-15 | Med-El电气医疗器械有限公司 | For the one-sided vocal cords pacemaker of paralysis automatically |
US9731131B2 (en) | 2011-12-07 | 2017-08-15 | Med-El Elektromedizinische Geraete Gmbh | Pacemaker for unilateral vocal cord autoparalysis |
US8630709B2 (en) * | 2011-12-07 | 2014-01-14 | Cyberonics, Inc. | Computer-implemented system and method for selecting therapy profiles of electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction |
US8918191B2 (en) * | 2011-12-07 | 2014-12-23 | Cyberonics, Inc. | Implantable device for providing electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction with bounded titration |
US8700150B2 (en) | 2012-01-17 | 2014-04-15 | Cyberonics, Inc. | Implantable neurostimulator for providing electrical stimulation of cervical vagus nerves for treatment of chronic cardiac dysfunction with bounded titration |
US8571654B2 (en) | 2012-01-17 | 2013-10-29 | Cyberonics, Inc. | Vagus nerve neurostimulator with multiple patient-selectable modes for treating chronic cardiac dysfunction |
US10973736B2 (en) | 2012-02-29 | 2021-04-13 | Frederick J. Muench | Systems, devices, components and methods for triggering or inducing resonance or high amplitude oscillations in a cardiovascular system of a patient |
US10098810B1 (en) | 2013-02-27 | 2018-10-16 | Frederick Muench | Systems, devices, components and methods for triggering or inducing resonance or high amplitude oscillations in a cardiovascular system of a patient |
US9943461B1 (en) | 2012-02-29 | 2018-04-17 | Frederick Muench | Systems, devices, components and methods for triggering or inducing resonance or high amplitude oscillations in a cardiovascular system of a patient |
US10632040B2 (en) | 2012-02-29 | 2020-04-28 | Frederick Muench | Systems, devices, components and methods for triggering or inducing resonance or high amplitude oscillations in a cardiovascular system of a patient |
US9572983B2 (en) | 2012-03-26 | 2017-02-21 | Setpoint Medical Corporation | Devices and methods for modulation of bone erosion |
US10448839B2 (en) | 2012-04-23 | 2019-10-22 | Livanova Usa, Inc. | Methods, systems and apparatuses for detecting increased risk of sudden death |
US9456916B2 (en) | 2013-03-12 | 2016-10-04 | Medibotics Llc | Device for selectively reducing absorption of unhealthy food |
US8688212B2 (en) | 2012-07-20 | 2014-04-01 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for managing bradycardia through vagus nerve stimulation |
EP2890449B1 (en) | 2012-08-31 | 2017-04-05 | Flint Hills Scientific, LLC | Contingent cardio-protection for epilepsy patients |
AU2013312785B2 (en) | 2012-09-05 | 2018-03-01 | ElectroCore, LLC | Non-invasive vagal nerve stimulation to treat disorders |
US9849025B2 (en) | 2012-09-07 | 2017-12-26 | Yale University | Brain cooling system |
US9452290B2 (en) | 2012-11-09 | 2016-09-27 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for managing tachyarrhythmia through vagus nerve stimulation |
US8923964B2 (en) | 2012-11-09 | 2014-12-30 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for enhancing heart failure patient awakening through vagus nerve stimulation |
US9643008B2 (en) | 2012-11-09 | 2017-05-09 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for enhancing post-exercise recovery through vagus nerve stimulation |
CN114768089A (en) | 2013-01-21 | 2022-07-22 | 卡拉健康公司 | Apparatus and method for controlling tremor |
US10220211B2 (en) | 2013-01-22 | 2019-03-05 | Livanova Usa, Inc. | Methods and systems to diagnose depression |
US10765884B1 (en) | 2013-02-27 | 2020-09-08 | Steven G Dean | Methods to trigger high amplitude oscillations or resonance in the cardiovascular system of a patient using electromagnetic stimulation |
US9610443B1 (en) | 2013-02-27 | 2017-04-04 | Steven G Dean | Methods to trigger high amplitude oscillations or resonance in the cardiovascular system of a patient using electrical stimulation |
US9011365B2 (en) | 2013-03-12 | 2015-04-21 | Medibotics Llc | Adjustable gastrointestinal bifurcation (AGB) for reduced absorption of unhealthy food |
US9067070B2 (en) | 2013-03-12 | 2015-06-30 | Medibotics Llc | Dysgeusia-inducing neurostimulation for modifying consumption of a selected nutrient type |
US9643011B2 (en) | 2013-03-14 | 2017-05-09 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for managing tachyarrhythmic risk during sleep through vagus nerve stimulation |
US9056195B2 (en) | 2013-03-15 | 2015-06-16 | Cyberonics, Inc. | Optimization of cranial nerve stimulation to treat seizure disorderse during sleep |
JP5345256B1 (en) | 2013-03-26 | 2013-11-20 | 謙輔 山川 | Electrical stimulator |
EP2796165B1 (en) | 2013-04-25 | 2016-04-20 | Sorin CRM SAS | Active implantable medical device for treating heart failure with vagus nerve stimulation synchronised with the heart activity |
FR3006596A1 (en) * | 2013-06-11 | 2014-12-12 | Sorin Crm Sas | ACTIVE IMPLANTABLE MEDICAL DEVICE FOR TREATMENT OF CARDIAC INSUFFICIENCY WITH STOCHASTIC STIMULATION OF WAVE NERVE |
US10124169B2 (en) * | 2013-06-28 | 2018-11-13 | Cyberonics, Inc. | Cranial nerve stimulation to treat seizure disorders |
EP2818199B1 (en) | 2013-06-30 | 2022-09-07 | Cyberonics, Inc. | Implantable vagal neurostimulator with bounded autotitration |
CN107569771B (en) * | 2013-08-26 | 2021-03-12 | 精能医学股份有限公司 | Electrical stimulator, stimulation method using same and electrical stimulation system |
US10413719B2 (en) * | 2016-04-15 | 2019-09-17 | Innovative Health Solutions, Inc. | Methods of treating disease using auricular peripheral nerve field stimulation |
US9999773B2 (en) | 2013-10-30 | 2018-06-19 | Cyberonics, Inc. | Implantable neurostimulator-implemented method utilizing multi-modal stimulation parameters |
US10779965B2 (en) | 2013-11-06 | 2020-09-22 | Enopace Biomedical Ltd. | Posts with compliant junctions |
CN103584840B (en) * | 2013-11-25 | 2015-05-27 | 天津大学 | Automatic sleep stage method based on electroencephalogram, heart rate variability and coherence between electroencephalogram and heart rate variability |
US9370659B2 (en) | 2013-12-05 | 2016-06-21 | Cardiac Pacemakers, Inc. | Intuited delivery of autonomic modulation therapy |
WO2015084774A1 (en) | 2013-12-05 | 2015-06-11 | Cardiac Pacemakers, Inc. | Dosed delivery of autonomic modulation therapy |
US9511228B2 (en) | 2014-01-14 | 2016-12-06 | Cyberonics, Inc. | Implantable neurostimulator-implemented method for managing hypertension through renal denervation and vagus nerve stimulation |
US9713719B2 (en) | 2014-04-17 | 2017-07-25 | Cyberonics, Inc. | Fine resolution identification of a neural fulcrum for the treatment of chronic cardiac dysfunction |
US9415224B2 (en) | 2014-04-25 | 2016-08-16 | Cyberonics, Inc. | Neurostimulation and recording of physiological response for the treatment of chronic cardiac dysfunction |
US9272143B2 (en) | 2014-05-07 | 2016-03-01 | Cyberonics, Inc. | Responsive neurostimulation for the treatment of chronic cardiac dysfunction |
US9409024B2 (en) | 2014-03-25 | 2016-08-09 | Cyberonics, Inc. | Neurostimulation in a neural fulcrum zone for the treatment of chronic cardiac dysfunction |
US9950169B2 (en) | 2014-04-25 | 2018-04-24 | Cyberonics, Inc. | Dynamic stimulation adjustment for identification of a neural fulcrum |
GB2525023B (en) * | 2014-04-10 | 2017-10-04 | Cardiola Ltd | Apparatus and method for treating a patient having a heart |
US9585611B2 (en) | 2014-04-25 | 2017-03-07 | Cyberonics, Inc. | Detecting seizures based on heartbeat data |
US9302109B2 (en) | 2014-04-25 | 2016-04-05 | Cyberonics, Inc. | Cranial nerve stimulation to treat depression during sleep |
US11311718B2 (en) | 2014-05-16 | 2022-04-26 | Aleva Neurotherapeutics Sa | Device for interacting with neurological tissue and methods of making and using the same |
EP3142745B1 (en) | 2014-05-16 | 2018-12-26 | Aleva Neurotherapeutics SA | Device for interacting with neurological tissue |
WO2015179567A1 (en) | 2014-05-20 | 2015-11-26 | The Regents Of The University Of California | Systems and methods for measuring cardiac timing from a ballistocardiogram |
EP4360697A1 (en) | 2014-06-02 | 2024-05-01 | Cala Health, Inc. | Systems and methods for peripheral nerve stimulation to treat tremor |
US9782584B2 (en) | 2014-06-13 | 2017-10-10 | Nervana, LLC | Transcutaneous electrostimulator and methods for electric stimulation |
US10130809B2 (en) | 2014-06-13 | 2018-11-20 | Nervana, LLC | Transcutaneous electrostimulator and methods for electric stimulation |
US9737716B2 (en) | 2014-08-12 | 2017-08-22 | Cyberonics, Inc. | Vagus nerve and carotid baroreceptor stimulation system |
US9770599B2 (en) | 2014-08-12 | 2017-09-26 | Cyberonics, Inc. | Vagus nerve stimulation and subcutaneous defibrillation system |
US9533153B2 (en) | 2014-08-12 | 2017-01-03 | Cyberonics, Inc. | Neurostimulation titration process |
US9403011B2 (en) | 2014-08-27 | 2016-08-02 | Aleva Neurotherapeutics | Leadless neurostimulator |
US9474894B2 (en) | 2014-08-27 | 2016-10-25 | Aleva Neurotherapeutics | Deep brain stimulation lead |
US11311725B2 (en) | 2014-10-24 | 2022-04-26 | Setpoint Medical Corporation | Systems and methods for stimulating and/or monitoring loci in the brain to treat inflammation and to enhance vagus nerve stimulation |
US9504832B2 (en) | 2014-11-12 | 2016-11-29 | Cyberonics, Inc. | Neurostimulation titration process via adaptive parametric modification |
KR101653889B1 (en) * | 2014-12-31 | 2016-09-09 | 영남대학교 산학협력단 | Active type trans-sacral implanted epidural pulsed radio frequency stimulator for spinal cord stimulation |
KR101653888B1 (en) * | 2014-12-31 | 2016-09-02 | 영남대학교 산학협력단 | Passive type trans-sacral implanted epidural pulsed radio frequency stimulator for spinal cord stimulation |
US11406833B2 (en) | 2015-02-03 | 2022-08-09 | Setpoint Medical Corporation | Apparatus and method for reminding, prompting, or alerting a patient with an implanted stimulator |
JP6452833B2 (en) * | 2015-02-04 | 2019-01-16 | ボストン サイエンティフィック ニューロモデュレイション コーポレイション | Method and apparatus for programming charge recovery in a neural stimulation waveform |
US10376308B2 (en) | 2015-02-05 | 2019-08-13 | Axon Therapies, Inc. | Devices and methods for treatment of heart failure by splanchnic nerve ablation |
US9956393B2 (en) | 2015-02-24 | 2018-05-01 | Elira, Inc. | Systems for increasing a delay in the gastric emptying time for a patient using a transcutaneous electro-dermal patch |
US10765863B2 (en) | 2015-02-24 | 2020-09-08 | Elira, Inc. | Systems and methods for using a transcutaneous electrical stimulation device to deliver titrated therapy |
US10864367B2 (en) | 2015-02-24 | 2020-12-15 | Elira, Inc. | Methods for using an electrical dermal patch in a manner that reduces adverse patient reactions |
US10376145B2 (en) | 2015-02-24 | 2019-08-13 | Elira, Inc. | Systems and methods for enabling a patient to achieve a weight loss objective using an electrical dermal patch |
US10335302B2 (en) | 2015-02-24 | 2019-07-02 | Elira, Inc. | Systems and methods for using transcutaneous electrical stimulation to enable dietary interventions |
CN115227969A (en) | 2015-02-24 | 2022-10-25 | 伊莱拉股份有限公司 | Method for achieving appetite regulation or improving dietary compliance using electrode patches |
US20220062621A1 (en) | 2015-02-24 | 2022-03-03 | Elira, Inc. | Electrical Stimulation-Based Weight Management System |
WO2016149176A1 (en) * | 2015-03-13 | 2016-09-22 | Case Western Reserve University | System for ensuring airway patency when asleep |
US9517344B1 (en) | 2015-03-13 | 2016-12-13 | Nevro Corporation | Systems and methods for selecting low-power, effective signal delivery parameters for an implanted pulse generator |
KR102427652B1 (en) | 2015-03-30 | 2022-08-01 | 세팔리 테크놀로지 에스피알엘 | Device for transdermal electrical stimulation of the trigeminal nerve |
US20160310740A1 (en) * | 2015-04-24 | 2016-10-27 | Guy P. Curtis | Method for stimulating heart muscle activity during the refractory period |
AU2016275135C1 (en) | 2015-06-10 | 2021-09-30 | Cala Health, Inc. | Systems and methods for peripheral nerve stimulation to treat tremor with detachable therapy and monitoring units |
CN108348746B (en) | 2015-09-23 | 2021-10-12 | 卡拉健康公司 | System and method for peripheral nerve stimulation in fingers or hands to treat hand tremor |
US10207110B1 (en) | 2015-10-13 | 2019-02-19 | Axon Therapies, Inc. | Devices and methods for treatment of heart failure via electrical modulation of a splanchnic nerve |
US11318310B1 (en) | 2015-10-26 | 2022-05-03 | Nevro Corp. | Neuromodulation for altering autonomic functions, and associated systems and methods |
US10596367B2 (en) | 2016-01-13 | 2020-03-24 | Setpoint Medical Corporation | Systems and methods for establishing a nerve block |
WO2017127758A1 (en) | 2016-01-20 | 2017-07-27 | Setpoint Medical Corporation | Implantable microstimulators and inductive charging systems |
US11471681B2 (en) | 2016-01-20 | 2022-10-18 | Setpoint Medical Corporation | Batteryless implantable microstimulators |
WO2017127756A1 (en) | 2016-01-20 | 2017-07-27 | Setpoint Medical Corporation | Control of vagal stimulation |
AU2017211048B2 (en) | 2016-01-21 | 2022-03-10 | Cala Health, Inc. | Systems, methods and devices for peripheral neuromodulation for treating diseases related to overactive bladder |
US10583304B2 (en) | 2016-01-25 | 2020-03-10 | Setpoint Medical Corporation | Implantable neurostimulator having power control and thermal regulation and methods of use |
EP3411111A1 (en) | 2016-02-02 | 2018-12-12 | Aleva Neurotherapeutics SA | Treatment of autoimmune diseases with deep brain stimulation |
US10070812B2 (en) * | 2016-03-03 | 2018-09-11 | SBB Research Group LLC | Method for improved seizure detection |
AU2017252643B2 (en) | 2016-04-19 | 2022-04-14 | Inspire Medical Systems, Inc. | Accelerometer-based sensing for sleep disordered breathing (SDB) care |
JP7077297B2 (en) | 2016-07-08 | 2022-05-30 | カラ ヘルス,インコーポレイテッド | Systems and methods for stimulating N nerves with strictly N electrodes and improved drywall |
CA3031766A1 (en) | 2016-07-29 | 2018-02-01 | Howard Levin | Devices, systems, and methods for treatment of heart failure by splanchnic nerve ablation |
US11813476B1 (en) * | 2016-12-16 | 2023-11-14 | Erchonia Corporation, Llc | Methods of treating the brain and nervous system using light therapy |
CN110809486A (en) | 2017-04-03 | 2020-02-18 | 卡拉健康公司 | Peripheral neuromodulation systems, methods, and devices for treating diseases associated with overactive bladder |
DE202018001803U1 (en) * | 2017-05-19 | 2018-06-27 | Cefaly Technology Sprl | External trigeminal nerve stimulation for the acute treatment of migraine attacks |
WO2019014250A1 (en) * | 2017-07-11 | 2019-01-17 | The General Hospital Corporation | Systems and methods for respiratory-gated nerve stimulation |
EP3668402A4 (en) | 2017-08-14 | 2021-05-19 | Setpoint Medical Corporation | Vagus nerve stimulation pre-screening test |
WO2019060298A1 (en) | 2017-09-19 | 2019-03-28 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement |
KR102495358B1 (en) * | 2017-09-25 | 2023-02-02 | 삼성전자주식회사 | Neuromimetic stimulating apparatus and method thereof |
EP3717062B1 (en) | 2017-11-29 | 2022-10-12 | Medtronic, Inc. | Tissue conduction communication between devices |
WO2019108742A1 (en) | 2017-11-29 | 2019-06-06 | Medtronic, Inc. | Device and method to reduce artifact from tissue conduction communication transmission |
US11110279B2 (en) | 2017-11-29 | 2021-09-07 | Medtronic, Inc. | Signal transmission optimization for tissue conduction communication |
CN111417431A (en) | 2017-11-29 | 2020-07-14 | 美敦力公司 | Tissue-conducted communication using ramped drive signals |
US11717686B2 (en) | 2017-12-04 | 2023-08-08 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to facilitate learning and performance |
WO2019118807A1 (en) | 2017-12-15 | 2019-06-20 | Medtronic, Inc. | Device, system and method with adaptive timing for tissue conduction communication transmission |
WO2019118976A1 (en) | 2017-12-17 | 2019-06-20 | Axon Therapies, Inc. | Methods and devices for endovascular ablation of a splanchnic nerve |
US11478603B2 (en) | 2017-12-31 | 2022-10-25 | Neuroenhancement Lab, LLC | Method and apparatus for neuroenhancement to enhance emotional response |
WO2019143790A1 (en) | 2018-01-17 | 2019-07-25 | Cala Health, Inc. | Systems and methods for treating inflammatory bowel disease through peripheral nerve stimulation |
JP7334167B2 (en) | 2018-01-26 | 2023-08-28 | アクソン セラピーズ,インク. | Method and device for endovascular ablation of visceral nerves |
US10702692B2 (en) | 2018-03-02 | 2020-07-07 | Aleva Neurotherapeutics | Neurostimulation device |
US20190299005A1 (en) | 2018-03-28 | 2019-10-03 | John Bienenstock | Vagus nerve stimulation and monitoring |
US11364361B2 (en) | 2018-04-20 | 2022-06-21 | Neuroenhancement Lab, LLC | System and method for inducing sleep by transplanting mental states |
GB201809890D0 (en) * | 2018-06-15 | 2018-08-01 | Emblation Ltd | Chronotherapeutic treatment profiling |
CN109259996B (en) * | 2018-09-03 | 2021-05-25 | 深圳市翔智达科技有限公司 | Massage robot, control method thereof, and computer-readable storage medium |
WO2020056418A1 (en) | 2018-09-14 | 2020-03-19 | Neuroenhancement Lab, LLC | System and method of improving sleep |
CN109171685B (en) * | 2018-09-20 | 2021-10-08 | 芯海科技(深圳)股份有限公司 | Method, device and storage medium for simulating human physiological signals |
US10835747B2 (en) | 2018-09-24 | 2020-11-17 | Vorso Corp. | Auricular nerve stimulation to address patient disorders, and associated systems and methods |
US11260229B2 (en) | 2018-09-25 | 2022-03-01 | The Feinstein Institutes For Medical Research | Methods and apparatuses for reducing bleeding via coordinated trigeminal and vagal nerve stimulation |
US11590352B2 (en) | 2019-01-29 | 2023-02-28 | Nevro Corp. | Ramped therapeutic signals for modulating inhibitory interneurons, and associated systems and methods |
CN110123342B (en) * | 2019-04-17 | 2021-06-08 | 西北大学 | Internet addiction detection method and system based on brain waves |
CN113825464A (en) | 2019-06-20 | 2021-12-21 | 阿克松疗法公司 | Method and apparatus for intravascular ablation of visceral nerves |
JP2022542581A (en) | 2019-07-25 | 2022-10-05 | インスパイア・メディカル・システムズ・インコーポレイテッド | Systems and methods for operating implantable medical devices based on sensed posture information |
US11890468B1 (en) | 2019-10-03 | 2024-02-06 | Cala Health, Inc. | Neurostimulation systems with event pattern detection and classification |
US11426599B2 (en) | 2019-11-22 | 2022-08-30 | Palo Alto Research Center Incorporated | Three-dimensional coil set used for neuromodulation |
US11413090B2 (en) | 2020-01-17 | 2022-08-16 | Axon Therapies, Inc. | Methods and devices for endovascular ablation of a splanchnic nerve |
US11452874B2 (en) | 2020-02-03 | 2022-09-27 | Medtronic, Inc. | Shape control for electrical stimulation therapy |
US11554264B2 (en) | 2020-04-24 | 2023-01-17 | Medtronic, Inc. | Electrode position detection |
KR20230012585A (en) | 2020-05-21 | 2023-01-26 | 더 파인스타인 인스티튜츠 포 메디칼 리서치 | Systems and methods for vagus nerve stimulation |
US11400299B1 (en) | 2021-09-14 | 2022-08-02 | Rainbow Medical Ltd. | Flexible antenna for stimulator |
WO2023157718A1 (en) * | 2022-02-18 | 2023-08-24 | ニプロ株式会社 | Medical device |
WO2023192485A1 (en) * | 2022-03-30 | 2023-10-05 | The Alfred E. Mann Foundation For Scientific Research | Automatic titration for vagus nerve stimulation |
CN116510181B (en) * | 2023-07-03 | 2023-09-08 | 科悦医疗(苏州)有限公司 | Vagus nerve stimulation system |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993021824A1 (en) * | 1992-04-24 | 1993-11-11 | Medtronic, Inc. | Implantable electrical vagal stimulation for prevention or interruption of life threatening arrhythmias |
US20040138721A1 (en) * | 1999-04-30 | 2004-07-15 | Medtronic, Inc. | Vagal nerve stimulation techniques for treatment of epileptic seizures |
EP1486232A2 (en) * | 2002-06-12 | 2004-12-15 | Pacesetter, Inc. | Device for improving cardiac funtion in heart failure or CHF patients |
US20050267542A1 (en) * | 2001-08-31 | 2005-12-01 | Biocontrol Medical Ltd. | Techniques for applying, configuring, and coordinating nerve fiber stimulation |
Family Cites Families (559)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1486232A (en) * | 1922-09-02 | 1924-03-11 | William F Cremean | Car-door arrangement |
US3760812A (en) | 1971-03-19 | 1973-09-25 | Univ Minnesota | Implantable spiral wound stimulation electrodes |
US3796221A (en) * | 1971-07-07 | 1974-03-12 | N Hagfors | Apparatus for delivering electrical stimulation energy to body-implanted apparatus with signal-receiving means |
US4073048A (en) * | 1976-07-30 | 1978-02-14 | A-Lok Corporation | Gasket seal between sewer pipe and manhole opening |
US4107469A (en) | 1977-02-17 | 1978-08-15 | Rockwell International Corporation | Multiplex/demultiplex apparatus |
JPS54119792A (en) | 1978-03-03 | 1979-09-17 | Iriyou Kougaku Kenkiyuushiyo K | Electric stimulation device for removing pain |
IT1118131B (en) | 1978-07-20 | 1986-02-24 | Medtronic Inc | IMPROVEMENT IN MULTI-MODE CARDIAC PACEMAKERS ADAPTABLE IMPLANTABLE |
US4431000A (en) | 1978-11-29 | 1984-02-14 | Gatron Corporation | Transcutaneous nerve stimulator with pseusorandom pulse generator |
US4503863A (en) | 1979-06-29 | 1985-03-12 | Katims Jefferson J | Method and apparatus for transcutaneous electrical stimulation |
US4305402A (en) | 1979-06-29 | 1981-12-15 | Katims Jefferson J | Method for transcutaneous electrical stimulation |
US4424812A (en) | 1980-10-09 | 1984-01-10 | Cordis Corporation | Implantable externally programmable microprocessor-controlled tissue stimulator |
US4459989A (en) | 1981-06-30 | 1984-07-17 | Neuromed, Inc. | Non-invasive multiprogrammable tissue stimulator and methods for use |
US4793353A (en) | 1981-06-30 | 1988-12-27 | Borkan William N | Non-invasive multiprogrammable tissue stimulator and method |
US4612934A (en) | 1981-06-30 | 1986-09-23 | Borkan William N | Non-invasive multiprogrammable tissue stimulator |
US4606349A (en) | 1981-08-10 | 1986-08-19 | Cordis Corporation | Implantable cardiac pacer having dual frequency programming and bipolar/unipolar lead programmability |
US4509946A (en) | 1982-09-23 | 1985-04-09 | Mcfarlane Richard H | Flow control device |
US4625308A (en) | 1982-11-30 | 1986-11-25 | American Satellite Company | All digital IDMA dynamic channel allocated satellite communications system and method |
CA1215128A (en) | 1982-12-08 | 1986-12-09 | Pedro Molina-Negro | Electric nerve stimulator device |
US4702254A (en) | 1983-09-14 | 1987-10-27 | Jacob Zabara | Neurocybernetic prosthesis |
US5025807A (en) | 1983-09-14 | 1991-06-25 | Jacob Zabara | Neurocybernetic prosthesis |
US4867164A (en) | 1983-09-14 | 1989-09-19 | Jacob Zabara | Neurocybernetic prosthesis |
US4577316A (en) * | 1984-02-13 | 1986-03-18 | Rca Corporation | Synchronization system for a regenerative subtransponder satellite communication system |
US4590946A (en) | 1984-06-14 | 1986-05-27 | Biomed Concepts, Inc. | Surgically implantable electrode for nerve bundles |
US4573481A (en) | 1984-06-25 | 1986-03-04 | Huntington Institute Of Applied Research | Implantable electrode array |
US4649936A (en) * | 1984-10-11 | 1987-03-17 | Case Western Reserve University | Asymmetric single electrode cuff for generation of unidirectionally propagating action potentials for collision blocking |
US4628942A (en) | 1984-10-11 | 1986-12-16 | Case Western Reserve University | Asymmetric shielded two electrode cuff |
US4608985A (en) | 1984-10-11 | 1986-09-02 | Case Western Reserve University | Antidromic pulse generating wave form for collision blocking |
US4592339A (en) | 1985-06-12 | 1986-06-03 | Mentor Corporation | Gastric banding device |
DE3822885C2 (en) | 1987-07-06 | 1994-06-01 | Asahi Optical Co Ltd | Optical cable and process for its manufacture |
US4949721A (en) | 1988-08-11 | 1990-08-21 | Omron Tateisi Electronics Co. | Transcutaneous electric nerve stimulater |
US4920979A (en) | 1988-10-12 | 1990-05-01 | Huntington Medical Research Institute | Bidirectional helical electrode for nerve stimulation |
EP0387363B1 (en) * | 1989-03-13 | 1994-06-01 | Pacesetter AB | Implantable stimulator whose intensity of stimulation of a physiologic event of living beings is adapted to their physical actvity |
US4977895A (en) | 1989-05-22 | 1990-12-18 | Ely Shavit Pasternak | Electrical apparatus for medical treatment |
US5210854A (en) | 1989-06-14 | 1993-05-11 | Digital Equipment Corporation | System for updating program stored in eeprom by storing new version into new location and updating second transfer vector to contain starting address of new version |
US5522865A (en) | 1989-09-22 | 1996-06-04 | Alfred E. Mann Foundation For Scientific Research | Voltage/current control system for a human tissue stimulator |
US4979511A (en) | 1989-11-03 | 1990-12-25 | Cyberonics, Inc. | Strain relief tether for implantable electrode |
US5179950A (en) | 1989-11-13 | 1993-01-19 | Cyberonics, Inc. | Implanted apparatus having micro processor controlled current and voltage sources with reduced voltage levels when not providing stimulation |
US5235980A (en) | 1989-11-13 | 1993-08-17 | Cyberonics, Inc. | Implanted apparatus disabling switching regulator operation to allow radio frequency signal reception |
US5186170A (en) | 1989-11-13 | 1993-02-16 | Cyberonics, Inc. | Simultaneous radio frequency and magnetic field microprocessor reset circuit |
US5154172A (en) | 1989-11-13 | 1992-10-13 | Cyberonics, Inc. | Constant current sources with programmable voltage source |
US5188104A (en) * | 1991-02-01 | 1993-02-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
US5263480A (en) | 1991-02-01 | 1993-11-23 | Cyberonics, Inc. | Treatment of eating disorders by nerve stimulation |
US5269303A (en) | 1991-02-22 | 1993-12-14 | Cyberonics, Inc. | Treatment of dementia by nerve stimulation |
US5215086A (en) | 1991-05-03 | 1993-06-01 | Cyberonics, Inc. | Therapeutic treatment of migraine symptoms by stimulation |
US5299569A (en) | 1991-05-03 | 1994-04-05 | Cyberonics, Inc. | Treatment of neuropsychiatric disorders by nerve stimulation |
US5335657A (en) | 1991-05-03 | 1994-08-09 | Cyberonics, Inc. | Therapeutic treatment of sleep disorder by nerve stimulation |
US5205285A (en) | 1991-06-14 | 1993-04-27 | Cyberonics, Inc. | Voice suppression of vagal stimulation |
US5150508A (en) * | 1991-06-28 | 1992-09-29 | E. R. St. Denis & Sons, Limited | Hemming machine and method |
WO1993001862A1 (en) | 1991-07-22 | 1993-02-04 | Cyberonics, Inc. | Treatment of respiratory disorders by nerve stimulation |
US5222494A (en) | 1991-07-31 | 1993-06-29 | Cyberonics, Inc. | Implantable tissue stimulator output stabilization system |
US5231988A (en) | 1991-08-09 | 1993-08-03 | Cyberonics, Inc. | Treatment of endocrine disorders by nerve stimulation |
WO1993002744A1 (en) | 1991-08-09 | 1993-02-18 | Cyberonics, Inc. | Treatment of anxiety disorders by nerve stimulation |
EP0532143A1 (en) | 1991-09-12 | 1993-03-17 | BIOTRONIK Mess- und Therapiegeräte GmbH & Co Ingenieurbüro Berlin | Neurostimulator |
US5304206A (en) | 1991-11-18 | 1994-04-19 | Cyberonics, Inc. | Activation techniques for implantable medical device |
US5203326A (en) * | 1991-12-18 | 1993-04-20 | Telectronics Pacing Systems, Inc. | Antiarrhythmia pacer using antiarrhythmia pacing and autonomic nerve stimulation therapy |
IT1259358B (en) | 1992-03-26 | 1996-03-12 | Sorin Biomedica Spa | IMPLANTABLE DEVICE FOR DETECTION AND CONTROL OF THE SYMPATHIC-VAGAL TONE |
GB9211085D0 (en) | 1992-05-23 | 1992-07-08 | Tippey Keith E | Electrical stimulation |
IT1260485B (en) | 1992-05-29 | 1996-04-09 | PROCEDURE AND DEVICE FOR THE TREATMENT OF THE OBESITY OF A PATIENT | |
US5330515A (en) | 1992-06-17 | 1994-07-19 | Cyberonics, Inc. | Treatment of pain by vagal afferent stimulation |
JP3476820B2 (en) | 1992-06-24 | 2003-12-10 | サイベロニクス,インク. | Treatment of dementia by nerve stimulation |
JP3493196B2 (en) | 1992-06-24 | 2004-02-03 | サイベロニクス,インク. | Treatment of neuropsychiatric disorders by nerve stimulation |
JPH07504597A (en) | 1992-06-30 | 1995-05-25 | メドトロニック インコーポレーテッド | Electrical medical stimulators and electrical stimulation methods |
EP0683657B2 (en) | 1993-02-10 | 2005-06-15 | Siemens Aktiengesellschaft | Apparatus for analgesic therapy and/or for influencing the vegetative nervous system |
US5411540A (en) | 1993-06-03 | 1995-05-02 | Massachusetts Institute Of Technology | Method and apparatus for preferential neuron stimulation |
US5411531A (en) | 1993-09-23 | 1995-05-02 | Medtronic, Inc. | Method and apparatus for control of A-V interval |
EP0688578B1 (en) | 1994-06-24 | 1999-11-10 | Pacesetter AB | Arrhythmia detector |
US5522862A (en) | 1994-09-21 | 1996-06-04 | Medtronic, Inc. | Method and apparatus for treating obstructive sleep apnea |
US5540734A (en) | 1994-09-28 | 1996-07-30 | Zabara; Jacob | Cranial nerve stimulation treatments using neurocybernetic prosthesis |
US5647379A (en) | 1994-11-22 | 1997-07-15 | Ventritex, Inc. | Correlator based electromagnetic interference responsive control system useful in medical devices |
US6132361A (en) | 1994-11-28 | 2000-10-17 | Neotonus, Inc. | Transcranial brain stimulation |
US6425852B1 (en) | 1994-11-28 | 2002-07-30 | Emory University | Apparatus and method for transcranial magnetic brain stimulation, including the treatment of depression and the localization and characterization of speech arrest |
US5571150A (en) | 1994-12-19 | 1996-11-05 | Cyberonics, Inc. | Treatment of patients in coma by nerve stimulation |
US5601617A (en) * | 1995-04-26 | 1997-02-11 | Advanced Bionics Corporation | Multichannel cochlear prosthesis with flexible control of stimulus waveforms |
US6219580B1 (en) | 1995-04-26 | 2001-04-17 | Advanced Bionics Corporation | Multichannel cochlear prosthesis with flexible control of stimulus waveforms |
US5540730A (en) | 1995-06-06 | 1996-07-30 | Cyberonics, Inc. | Treatment of motility disorders by nerve stimulation |
US5707400A (en) * | 1995-09-19 | 1998-01-13 | Cyberonics, Inc. | Treating refractory hypertension by nerve stimulation |
US5700282A (en) | 1995-10-13 | 1997-12-23 | Zabara; Jacob | Heart rhythm stabilization using a neurocybernetic prosthesis |
US6480743B1 (en) | 2000-04-05 | 2002-11-12 | Neuropace, Inc. | System and method for adaptive brain stimulation |
US6944501B1 (en) | 2000-04-05 | 2005-09-13 | Neurospace, Inc. | Neurostimulator involving stimulation strategies and process for using it |
US5755750A (en) | 1995-11-13 | 1998-05-26 | University Of Florida | Method and apparatus for selectively inhibiting activity in nerve fibers |
US6073048A (en) | 1995-11-17 | 2000-06-06 | Medtronic, Inc. | Baroreflex modulation with carotid sinus nerve stimulation for the treatment of heart failure |
US5995868A (en) | 1996-01-23 | 1999-11-30 | University Of Kansas | System for the prediction, rapid detection, warning, prevention, or control of changes in activity states in the brain of a subject |
US6463328B1 (en) | 1996-02-02 | 2002-10-08 | Michael Sasha John | Adaptive brain stimulation method and system |
US5611350A (en) * | 1996-02-08 | 1997-03-18 | John; Michael S. | Method and apparatus for facilitating recovery of patients in deep coma |
US5913876A (en) | 1996-02-20 | 1999-06-22 | Cardiothoracic Systems, Inc. | Method and apparatus for using vagus nerve stimulation in surgery |
US5651378A (en) | 1996-02-20 | 1997-07-29 | Cardiothoracic Systems, Inc. | Method of using vagal nerve stimulation in surgery |
US6051017A (en) * | 1996-02-20 | 2000-04-18 | Advanced Bionics Corporation | Implantable microstimulator and systems employing the same |
US5690681A (en) | 1996-03-29 | 1997-11-25 | Purdue Research Foundation | Method and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation |
WO1997036646A1 (en) | 1996-04-01 | 1997-10-09 | Valery Ivanovich Kobozev | Electrical gastro-intestinal tract stimulator |
US5702429A (en) | 1996-04-04 | 1997-12-30 | Medtronic, Inc. | Neural stimulation techniques with feedback |
US6006134A (en) | 1998-04-30 | 1999-12-21 | Medtronic, Inc. | Method and device for electronically controlling the beating of a heart using venous electrical stimulation of nerve fibers |
US6628987B1 (en) | 2000-09-26 | 2003-09-30 | Medtronic, Inc. | Method and system for sensing cardiac contractions during vagal stimulation-induced cardiopalegia |
US6532388B1 (en) * | 1996-04-30 | 2003-03-11 | Medtronic, Inc. | Method and system for endotracheal/esophageal stimulation prior to and during a medical procedure |
US5690691A (en) | 1996-05-08 | 1997-11-25 | The Center For Innovative Technology | Gastro-intestinal pacemaker having phased multi-point stimulation |
AU3304997A (en) * | 1996-05-31 | 1998-01-05 | Southern Illinois University | Methods of modulating aspects of brain neural plasticity by vagus nerve stimulation |
US6609031B1 (en) | 1996-06-07 | 2003-08-19 | Advanced Neuromodulation Systems, Inc. | Multiprogrammable tissue stimulator and method |
US6246912B1 (en) | 1996-06-27 | 2001-06-12 | Sherwood Services Ag | Modulated high frequency tissue modification |
US5800474A (en) | 1996-11-01 | 1998-09-01 | Medtronic, Inc. | Method of controlling epilepsy by brain stimulation |
US5690688A (en) | 1996-11-12 | 1997-11-25 | Pacesetter Ab | Medical therapy apparatus which administers therapy adjusted to follow natural variability of the physiological function being controlled |
EP0944411B1 (en) | 1996-12-12 | 2001-04-25 | Intermedics Inc. | Implantable medical device responsive to heart rate variability analysis |
AR010696A1 (en) | 1996-12-12 | 2000-06-28 | Sasol Tech Pty Ltd | A METHOD FOR THE ELIMINATION OF CARBON DIOXIDE FROM A PROCESS GAS |
DE69612628D1 (en) * | 1996-12-12 | 2001-05-31 | Intermedics Inc | IMPLANTABLE MEDICAL DEVICE FOR ANALYZING CARDIAC RATIO DEVIATIONS |
US7630757B2 (en) | 1997-01-06 | 2009-12-08 | Flint Hills Scientific Llc | System for the prediction, rapid detection, warning, prevention, or control of changes in activity states in the brain of a subject |
US6026326A (en) | 1997-01-13 | 2000-02-15 | Medtronic, Inc. | Apparatus and method for treating chronic constipation |
EP1666087A3 (en) | 1997-02-26 | 2009-04-29 | The Alfred E Mann Foundation for Scientific Research | Battery-powered patient implantable device |
US5792212A (en) | 1997-03-07 | 1998-08-11 | Medtronic, Inc. | Nerve evoked potential measurement system using chaotic sequences for noise rejection |
US5861014A (en) | 1997-04-30 | 1999-01-19 | Medtronic, Inc. | Method and apparatus for sensing a stimulating gastrointestinal tract on-demand |
US5836994A (en) | 1997-04-30 | 1998-11-17 | Medtronic, Inc. | Method and apparatus for electrical stimulation of the gastrointestinal tract |
US5954752A (en) * | 1997-04-30 | 1999-09-21 | Medtronic, Inc. | Cardioversion energy reduction system |
EP0786654A3 (en) * | 1997-05-07 | 1997-12-10 | Martin Lehmann | Installation for leak testing of containers |
IT1292016B1 (en) | 1997-05-28 | 1999-01-25 | Valerio Cigaina | IMPLANT DEVICE PARTICULARLY FOR ELECTROSTIMULATION AND / OR ELECTRO-REGISTRATION OF ENDOABDOMINAL VISCERS |
US6104959A (en) | 1997-07-31 | 2000-08-15 | Microwave Medical Corp. | Method and apparatus for treating subcutaneous histological features |
JP2001513495A (en) | 1997-08-08 | 2001-09-04 | デューク ユニバーシティ | Compositions, devices and methods that facilitate surgical procedures |
US6479523B1 (en) | 1997-08-26 | 2002-11-12 | Emory University | Pharmacologic drug combination in vagal-induced asystole |
US6631293B2 (en) | 1997-09-15 | 2003-10-07 | Cardiac Pacemakers, Inc. | Method for monitoring end of life for battery |
US6141590A (en) * | 1997-09-25 | 2000-10-31 | Medtronic, Inc. | System and method for respiration-modulated pacing |
US6409674B1 (en) | 1998-09-24 | 2002-06-25 | Data Sciences International, Inc. | Implantable sensor with wireless communication |
US5941906A (en) | 1997-10-15 | 1999-08-24 | Medtronic, Inc. | Implantable, modular tissue stimulator |
US6597954B1 (en) | 1997-10-27 | 2003-07-22 | Neuropace, Inc. | System and method for controlling epileptic seizures with spatially separated detection and stimulation electrodes |
US6459936B2 (en) | 1997-10-27 | 2002-10-01 | Neuropace, Inc. | Methods for responsively treating neurological disorders |
US6016449A (en) | 1997-10-27 | 2000-01-18 | Neuropace, Inc. | System for treatment of neurological disorders |
US6354299B1 (en) | 1997-10-27 | 2002-03-12 | Neuropace, Inc. | Implantable device for patient communication |
US6104955A (en) | 1997-12-15 | 2000-08-15 | Medtronic, Inc. | Method and apparatus for electrical stimulation of the gastrointestinal tract |
US6070100A (en) | 1997-12-15 | 2000-05-30 | Medtronic Inc. | Pacing system for optimizing cardiac output and determining heart condition |
US6078838A (en) | 1998-02-13 | 2000-06-20 | University Of Iowa Research Foundation | Pseudospontaneous neural stimulation system and method |
US6221908B1 (en) | 1998-03-12 | 2001-04-24 | Scientific Learning Corporation | System for stimulating brain plasticity |
US6374140B1 (en) | 1998-04-30 | 2002-04-16 | Medtronic, Inc. | Method and apparatus for treating seizure disorders by stimulating the olfactory senses |
US5928272A (en) | 1998-05-02 | 1999-07-27 | Cyberonics, Inc. | Automatic activation of a neurostimulator device using a detection algorithm based on cardiac activity |
US6463327B1 (en) | 1998-06-11 | 2002-10-08 | Cprx Llc | Stimulatory device and methods to electrically stimulate the phrenic nerve |
US6477424B1 (en) | 1998-06-19 | 2002-11-05 | Medtronic, Inc. | Medical management system integrated programming apparatus for communication with an implantable medical device |
US7209787B2 (en) | 1998-08-05 | 2007-04-24 | Bioneuronics Corporation | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US7242984B2 (en) | 1998-08-05 | 2007-07-10 | Neurovista Corporation | Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease |
US7231254B2 (en) | 1998-08-05 | 2007-06-12 | Bioneuronics Corporation | Closed-loop feedback-driven neuromodulation |
US6366813B1 (en) | 1998-08-05 | 2002-04-02 | Dilorenzo Daniel J. | Apparatus and method for closed-loop intracranical stimulation for optimal control of neurological disease |
US8762065B2 (en) | 1998-08-05 | 2014-06-24 | Cyberonics, Inc. | Closed-loop feedback-driven neuromodulation |
US9375573B2 (en) | 1998-08-05 | 2016-06-28 | Cyberonics, Inc. | Systems and methods for monitoring a patient's neurological disease state |
US9113801B2 (en) | 1998-08-05 | 2015-08-25 | Cyberonics, Inc. | Methods and systems for continuous EEG monitoring |
US7277758B2 (en) * | 1998-08-05 | 2007-10-02 | Neurovista Corporation | Methods and systems for predicting future symptomatology in a patient suffering from a neurological or psychiatric disorder |
US7747325B2 (en) | 1998-08-05 | 2010-06-29 | Neurovista Corporation | Systems and methods for monitoring a patient's neurological disease state |
US6249704B1 (en) | 1998-08-11 | 2001-06-19 | Advanced Bionics Corporation | Low voltage stimulation to elicit stochastic response patterns that enhance the effectiveness of a cochlear implant |
US6615081B1 (en) | 1998-10-26 | 2003-09-02 | Birinder R. Boveja | Apparatus and method for adjunct (add-on) treatment of diabetes by neuromodulation with an external stimulator |
US20030212440A1 (en) | 2002-05-09 | 2003-11-13 | Boveja Birinder R. | Method and system for modulating the vagus nerve (10th cranial nerve) using modulated electrical pulses with an inductively coupled stimulation system |
US6366814B1 (en) | 1998-10-26 | 2002-04-02 | Birinder R. Boveja | External stimulator for adjunct (add-on) treatment for neurological, neuropsychiatric, and urological disorders |
US6564102B1 (en) | 1998-10-26 | 2003-05-13 | Birinder R. Boveja | Apparatus and method for adjunct (add-on) treatment of coma and traumatic brain injury with neuromodulation using an external stimulator |
US6668191B1 (en) | 1998-10-26 | 2003-12-23 | Birinder R. Boveja | Apparatus and method for electrical stimulation adjunct (add-on) therapy of atrial fibrillation, inappropriate sinus tachycardia, and refractory hypertension with an external stimulator |
US6269270B1 (en) | 1998-10-26 | 2001-07-31 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy of Dementia and Alzheimer's disease utilizing an implantable lead and external stimulator |
US7076307B2 (en) * | 2002-05-09 | 2006-07-11 | Boveja Birinder R | Method and system for modulating the vagus nerve (10th cranial nerve) with electrical pulses using implanted and external components, to provide therapy neurological and neuropsychiatric disorders |
US6505074B2 (en) | 1998-10-26 | 2003-01-07 | Birinder R. Boveja | Method and apparatus for electrical stimulation adjunct (add-on) treatment of urinary incontinence and urological disorders using an external stimulator |
US6356788B2 (en) * | 1998-10-26 | 2002-03-12 | Birinder Bob Boveja | Apparatus and method for adjunct (add-on) therapy for depression, migraine, neuropsychiatric disorders, partial complex epilepsy, generalized epilepsy and involuntary movement disorders utilizing an external stimulator |
US6611715B1 (en) | 1998-10-26 | 2003-08-26 | Birinder R. Boveja | Apparatus and method for neuromodulation therapy for obesity and compulsive eating disorders using an implantable lead-receiver and an external stimulator |
US6253109B1 (en) | 1998-11-05 | 2001-06-26 | Medtronic Inc. | System for optimized brain stimulation |
US6161044A (en) | 1998-11-23 | 2000-12-12 | Synaptic Corporation | Method and apparatus for treating chronic pain syndromes, tremor, dementia and related disorders and for inducing electroanesthesia using high frequency, high intensity transcutaneous electrical nerve stimulation |
US6155267A (en) | 1998-12-31 | 2000-12-05 | Medtronic, Inc. | Implantable medical device monitoring method and system regarding same |
US6115628A (en) | 1999-03-29 | 2000-09-05 | Medtronic, Inc. | Method and apparatus for filtering electrocardiogram (ECG) signals to remove bad cycle information and for use of physiologic signals determined from said filtered ECG signals |
US6324421B1 (en) | 1999-03-29 | 2001-11-27 | Medtronic, Inc. | Axis shift analysis of electrocardiogram signal parameters especially applicable for multivector analysis by implantable medical devices, and use of same |
US6115627A (en) * | 1999-04-09 | 2000-09-05 | Pacesetter, Inc. | Intracardiac predictor of imminent arrhythmia |
US6684104B2 (en) * | 1999-04-14 | 2004-01-27 | Transneuronix, Inc. | Gastric stimulator apparatus and method for installing |
US6895278B1 (en) | 1999-04-14 | 2005-05-17 | Transneuronix, Inc. | Gastric stimulator apparatus and method for use |
US6190324B1 (en) | 1999-04-28 | 2001-02-20 | Medtronic, Inc. | Implantable medical device for tracking patient cardiac status |
US6579280B1 (en) | 1999-04-30 | 2003-06-17 | Medtronic, Inc. | Generic multi-step therapeutic treatment protocol |
US6353762B1 (en) * | 1999-04-30 | 2002-03-05 | Medtronic, Inc. | Techniques for selective activation of neurons in the brain, spinal cord parenchyma or peripheral nerve |
US6748275B2 (en) | 1999-05-05 | 2004-06-08 | Respironics, Inc. | Vestibular stimulation system and method |
US6312378B1 (en) * | 1999-06-03 | 2001-11-06 | Cardiac Intelligence Corporation | System and method for automated collection and analysis of patient information retrieved from an implantable medical device for remote patient care |
US6167311A (en) | 1999-06-14 | 2000-12-26 | Electro Core Techniques, Llc | Method of treating psychological disorders by brain stimulation within the thalamus |
US7991625B2 (en) | 1999-06-23 | 2011-08-02 | Koninklijke Philips Electronics N.V. | System for providing expert care to a basic care medical facility from a remote location |
US7454359B2 (en) | 1999-06-23 | 2008-11-18 | Visicu, Inc. | System and method for displaying a health status of hospitalized patients |
US6587719B1 (en) | 1999-07-01 | 2003-07-01 | Cyberonics, Inc. | Treatment of obesity by bilateral vagus nerve stimulation |
US20020052539A1 (en) | 1999-07-07 | 2002-05-02 | Markus Haller | System and method for emergency communication between an implantable medical device and a remote computer system or health care provider |
US6188929B1 (en) * | 1999-07-15 | 2001-02-13 | Joseph Giordano | Sequentially generated multi-parameter bio-electric delivery system and method |
US6298271B1 (en) | 1999-07-19 | 2001-10-02 | Medtronic, Inc. | Medical system having improved telemetry |
US6820019B1 (en) | 1999-07-31 | 2004-11-16 | Medtronic, Inc. | Device and method for determining and communicating the remaining life of a battery in an implantable neurological tissue stimulating device |
US6304775B1 (en) | 1999-09-22 | 2001-10-16 | Leonidas D. Iasemidis | Seizure warning and prediction |
US6308102B1 (en) | 1999-09-29 | 2001-10-23 | Stimsoft, Inc. | Patient interactive neurostimulation system and method |
US6381496B1 (en) | 1999-10-01 | 2002-04-30 | Advanced Bionics Corporation | Parameter context switching for an implanted device |
US20030095648A1 (en) | 1999-10-05 | 2003-05-22 | Lifecor, Inc. | Fault-tolerant remote reprogramming for a patient-worn medical device |
US6560486B1 (en) | 1999-10-12 | 2003-05-06 | Ivan Osorio | Bi-directional cerebral interface system |
US6473644B1 (en) | 1999-10-13 | 2002-10-29 | Cyberonics, Inc. | Method to enhance cardiac capillary growth in heart failure patients |
US6764498B2 (en) | 1999-12-09 | 2004-07-20 | Hans Alois Mische | Methods and devices for treatment of neurological disorders |
US6853862B1 (en) | 1999-12-03 | 2005-02-08 | Medtronic, Inc. | Gastroelectric stimulation for influencing pancreatic secretions |
US20030208212A1 (en) | 1999-12-07 | 2003-11-06 | Valerio Cigaina | Removable gastric band |
CA2397607A1 (en) | 1999-12-17 | 2001-06-21 | Carla M. Mann | Magnitude programming for implantable electrical stimulator |
US20010037220A1 (en) | 1999-12-21 | 2001-11-01 | Merry Randy L. | Integrated software system for implantable medical device installation and management |
US20050240246A1 (en) | 1999-12-24 | 2005-10-27 | Medtronic, Inc. | Large-scale processing loop for implantable medical devices |
US7483743B2 (en) | 2000-01-11 | 2009-01-27 | Cedars-Sinai Medical Center | System for detecting, diagnosing, and treating cardiovascular disease |
US6885888B2 (en) | 2000-01-20 | 2005-04-26 | The Cleveland Clinic Foundation | Electrical stimulation of the sympathetic nerve chain |
US20060085046A1 (en) | 2000-01-20 | 2006-04-20 | Ali Rezai | Methods of treating medical conditions by transvascular neuromodulation of the autonomic nervous system |
US6438423B1 (en) | 2000-01-20 | 2002-08-20 | Electrocore Technique, Llc | Method of treating complex regional pain syndromes by electrical stimulation of the sympathetic nerve chain |
US6811534B2 (en) | 2000-01-21 | 2004-11-02 | Medtronic Minimed, Inc. | Ambulatory medical apparatus and method using a telemetry system with predefined reception listening periods |
US6600953B2 (en) | 2000-12-11 | 2003-07-29 | Impulse Dynamics N.V. | Acute and chronic electrical signal therapy for obesity |
DE10002932A1 (en) | 2000-01-25 | 2001-07-26 | Biotronik Mess & Therapieg | Medical device implant |
US6708064B2 (en) * | 2000-02-24 | 2004-03-16 | Ali R. Rezai | Modulation of the brain to affect psychiatric disorders |
US6418344B1 (en) | 2000-02-24 | 2002-07-09 | Electrocore Techniques, Llc | Method of treating psychiatric disorders by electrical stimulation within the orbitofrontal cerebral cortex |
US6609030B1 (en) | 2000-02-24 | 2003-08-19 | Electrocore Techniques, Llc | Method of treating psychiatric diseases by neuromodulation within the dorsomedial thalamus |
US6473639B1 (en) | 2000-03-02 | 2002-10-29 | Neuropace, Inc. | Neurological event detection procedure using processed display channel based algorithms and devices incorporating these procedures |
US6484132B1 (en) | 2000-03-07 | 2002-11-19 | Lockheed Martin Energy Research Corporation | Condition assessment of nonlinear processes |
US7831301B2 (en) | 2001-03-16 | 2010-11-09 | Medtronic, Inc. | Heart failure monitor quicklook summary for patient management systems |
US6612983B1 (en) | 2000-03-28 | 2003-09-02 | Medtronic, Inc. | Pancreatic secretion response to stimulation test protocol |
US6768969B1 (en) | 2000-04-03 | 2004-07-27 | Flint Hills Scientific, L.L.C. | Method, computer program, and system for automated real-time signal analysis for detection, quantification, and prediction of signal changes |
US6466822B1 (en) | 2000-04-05 | 2002-10-15 | Neuropace, Inc. | Multimodal neurostimulator and process of using it |
US6826428B1 (en) | 2000-04-11 | 2004-11-30 | The Board Of Regents Of The University Of Texas System | Gastrointestinal electrical stimulation |
DE10018360C2 (en) | 2000-04-13 | 2002-10-10 | Cochlear Ltd | At least partially implantable system for the rehabilitation of a hearing impairment |
US7082333B1 (en) | 2000-04-27 | 2006-07-25 | Medtronic, Inc. | Patient directed therapy management |
US6522928B2 (en) | 2000-04-27 | 2003-02-18 | Advanced Bionics Corporation | Physiologically based adjustment of stimulation parameters to an implantable electronic stimulator to reduce data transmission rate |
US6737875B2 (en) | 2000-05-22 | 2004-05-18 | Damerco, Inc. | Method and apparatus for in-circuit impedance measurement |
US6610713B2 (en) | 2000-05-23 | 2003-08-26 | North Shore - Long Island Jewish Research Institute | Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation |
US7485095B2 (en) | 2000-05-30 | 2009-02-03 | Vladimir Shusterman | Measurement and analysis of trends in physiological and/or health data |
DE60018556T2 (en) | 2000-07-11 | 2006-03-02 | Sorin Biomedica Crm S.R.L., Saluggia | Implantable pacemaker with automatic mode switching controlled by sympatho-vagal matching |
US7756584B2 (en) | 2000-07-13 | 2010-07-13 | Advanced Neuromodulation Systems, Inc. | Methods and apparatus for effectuating a lasting change in a neural-function of a patient |
US20040176831A1 (en) | 2000-07-13 | 2004-09-09 | Gliner Bradford Evan | Apparatuses and systems for applying electrical stimulation to a patient |
US7672730B2 (en) * | 2001-03-08 | 2010-03-02 | Advanced Neuromodulation Systems, Inc. | Methods and apparatus for effectuating a lasting change in a neural-function of a patient |
US7305268B2 (en) * | 2000-07-13 | 2007-12-04 | Northstar Neurscience, Inc. | Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators |
US7146217B2 (en) | 2000-07-13 | 2006-12-05 | Northstar Neuroscience, Inc. | Methods and apparatus for effectuating a change in a neural-function of a patient |
US7236831B2 (en) * | 2000-07-13 | 2007-06-26 | Northstar Neuroscience, Inc. | Methods and apparatus for effectuating a lasting change in a neural-function of a patient |
US7831305B2 (en) | 2001-10-15 | 2010-11-09 | Advanced Neuromodulation Systems, Inc. | Neural stimulation system and method responsive to collateral neural activity |
US7010351B2 (en) | 2000-07-13 | 2006-03-07 | Northstar Neuroscience, Inc. | Methods and apparatus for effectuating a lasting change in a neural-function of a patient |
US20030125786A1 (en) | 2000-07-13 | 2003-07-03 | Gliner Bradford Evan | Methods and apparatus for effectuating a lasting change in a neural-function of a patient |
US7024247B2 (en) | 2001-10-15 | 2006-04-04 | Northstar Neuroscience, Inc. | Systems and methods for reducing the likelihood of inducing collateral neural activity during neural stimulation threshold test procedures |
US20050021118A1 (en) * | 2000-07-13 | 2005-01-27 | Chris Genau | Apparatuses and systems for applying electrical stimulation to a patient |
US6662053B2 (en) | 2000-08-17 | 2003-12-09 | William N. Borkan | Multichannel stimulator electronics and methods |
DE60136962D1 (en) | 2000-08-22 | 2009-01-22 | Medtronic Inc | NETWORK-IMPLEMENTED MEDICAL SYSTEMS FOR REMOTE PATIENT MANAGEMENT |
US7685005B2 (en) | 2000-08-29 | 2010-03-23 | Medtronic, Inc. | Medical device systems implemented network scheme for remote patient management |
US6591138B1 (en) | 2000-08-31 | 2003-07-08 | Neuropace, Inc. | Low frequency neurostimulator for the treatment of neurological disorders |
US6487446B1 (en) * | 2000-09-26 | 2002-11-26 | Medtronic, Inc. | Method and system for spinal cord stimulation prior to and during a medical procedure |
US7623926B2 (en) * | 2000-09-27 | 2009-11-24 | Cvrx, Inc. | Stimulus regimens for cardiovascular reflex control |
US7499742B2 (en) * | 2001-09-26 | 2009-03-03 | Cvrx, Inc. | Electrode structures and methods for their use in cardiovascular reflex control |
US6615084B1 (en) | 2000-11-15 | 2003-09-02 | Transneuronix, Inc. | Process for electrostimulation treatment of morbid obesity |
US6832114B1 (en) | 2000-11-21 | 2004-12-14 | Advanced Bionics Corporation | Systems and methods for modulation of pancreatic endocrine secretion and treatment of diabetes |
US6594524B2 (en) | 2000-12-12 | 2003-07-15 | The Trustees Of The University Of Pennsylvania | Adaptive method and apparatus for forecasting and controlling neurological disturbances under a multi-level control |
US6609025B2 (en) | 2001-01-02 | 2003-08-19 | Cyberonics, Inc. | Treatment of obesity by bilateral sub-diaphragmatic nerve stimulation |
US6788975B1 (en) | 2001-01-30 | 2004-09-07 | Advanced Bionics Corporation | Fully implantable miniature neurostimulator for stimulation as a therapy for epilepsy |
US6754536B2 (en) | 2001-01-31 | 2004-06-22 | Medtronic, Inc | Implantable medical device affixed internally within the gastrointestinal tract |
US6949929B2 (en) | 2003-06-24 | 2005-09-27 | Biophan Technologies, Inc. | Magnetic resonance imaging interference immune device |
US6775573B2 (en) | 2001-03-01 | 2004-08-10 | Science Medicus Inc. | Electrical method to control autonomic nerve stimulation of gastrointestinal tract |
US7299096B2 (en) | 2001-03-08 | 2007-11-20 | Northstar Neuroscience, Inc. | System and method for treating Parkinson's Disease and other movement disorders |
US6901292B2 (en) | 2001-03-19 | 2005-05-31 | Medtronic, Inc. | Control of externally induced current in an implantable pulse generator |
AU2002309179B2 (en) * | 2001-04-05 | 2006-10-19 | Med-El Elektromedizinische Gerate Ges.M.B.H. | Pacemaker for bilateral vocal cord autoparalysis |
US6477417B1 (en) | 2001-04-12 | 2002-11-05 | Pacesetter, Inc. | System and method for automatically selecting electrode polarity during sensing and stimulation |
US7369897B2 (en) | 2001-04-19 | 2008-05-06 | Neuro And Cardiac Technologies, Llc | Method and system of remotely controlling electrical pulses provided to nerve tissue(s) by an implanted stimulator system for neuromodulation therapies |
US6907295B2 (en) | 2001-08-31 | 2005-06-14 | Biocontrol Medical Ltd. | Electrode assembly for nerve control |
US6684105B2 (en) | 2001-08-31 | 2004-01-27 | Biocontrol Medical, Ltd. | Treatment of disorders by unidirectional nerve stimulation |
US6671555B2 (en) | 2001-04-27 | 2003-12-30 | Medtronic, Inc. | Closed loop neuromodulation for suppression of epileptic activity |
DE60214698T2 (en) | 2001-04-30 | 2007-09-13 | Medtronic, Inc., Minneapolis | IMPLANTABLE MEDICAL DEVICE AND PLASTER SYSTEM |
US6656125B2 (en) | 2001-06-01 | 2003-12-02 | Dale Julian Misczynski | System and process for analyzing a medical condition of a user |
US6671547B2 (en) | 2001-06-13 | 2003-12-30 | Koninklijke Philips Electronics N.V. | Adaptive analysis method for an electrotherapy device and apparatus |
US6622038B2 (en) | 2001-07-28 | 2003-09-16 | Cyberonics, Inc. | Treatment of movement disorders by near-diaphragmatic nerve stimulation |
US6622047B2 (en) | 2001-07-28 | 2003-09-16 | Cyberonics, Inc. | Treatment of neuropsychiatric disorders by near-diaphragmatic nerve stimulation |
US20040036377A1 (en) * | 2001-08-15 | 2004-02-26 | Steven Mezinis | High voltage lc electric and magnetic field motivator |
US6622041B2 (en) * | 2001-08-21 | 2003-09-16 | Cyberonics, Inc. | Treatment of congestive heart failure and autonomic cardiovascular drive disorders |
US6760626B1 (en) | 2001-08-29 | 2004-07-06 | Birinder R. Boveja | Apparatus and method for treatment of neurological and neuropsychiatric disorders using programmerless implantable pulse generator system |
US6449512B1 (en) | 2001-08-29 | 2002-09-10 | Birinder R. Boveja | Apparatus and method for treatment of urological disorders using programmerless implantable pulse generator system |
US7054686B2 (en) | 2001-08-30 | 2006-05-30 | Biophan Technologies, Inc. | Pulsewidth electrical stimulation |
US6731979B2 (en) | 2001-08-30 | 2004-05-04 | Biophan Technologies Inc. | Pulse width cardiac pacing apparatus |
US7885709B2 (en) | 2001-08-31 | 2011-02-08 | Bio Control Medical (B.C.M.) Ltd. | Nerve stimulation for treating disorders |
US7778703B2 (en) * | 2001-08-31 | 2010-08-17 | Bio Control Medical (B.C.M.) Ltd. | Selective nerve fiber stimulation for treating heart conditions |
US7778711B2 (en) | 2001-08-31 | 2010-08-17 | Bio Control Medical (B.C.M.) Ltd. | Reduction of heart rate variability by parasympathetic stimulation |
WO2003026738A1 (en) | 2001-09-28 | 2003-04-03 | Northstar Neuroscience, Inc. | Methods and apparatus for electrically stimulating cells implanted in the nervous system |
US20050137480A1 (en) | 2001-10-01 | 2005-06-23 | Eckhard Alt | Remote control of implantable device through medical implant communication service band |
US6671552B2 (en) * | 2001-10-02 | 2003-12-30 | Medtronic, Inc. | System and method for determining remaining battery life for an implantable medical device |
US6840904B2 (en) * | 2001-10-11 | 2005-01-11 | Jason Goldberg | Medical monitoring device and system |
US7904161B2 (en) | 2001-10-22 | 2011-03-08 | Oscor Inc. | Lead adaptor having low resistance conductors and/or encapsulated housing |
US6934583B2 (en) | 2001-10-22 | 2005-08-23 | Pacesetter, Inc. | Implantable lead and method for stimulating the vagus nerve |
US20030083716A1 (en) | 2001-10-23 | 2003-05-01 | Nicolelis Miguel A.L. | Intelligent brain pacemaker for real-time monitoring and controlling of epileptic seizures |
US20030109903A1 (en) | 2001-12-12 | 2003-06-12 | Epic Biosonics Inc. | Low profile subcutaneous enclosure |
US7050856B2 (en) | 2002-01-11 | 2006-05-23 | Medtronic, Inc. | Variation of neural-stimulation parameters |
EP1465713B1 (en) | 2002-01-18 | 2008-04-02 | mamutec AG | Sling |
US20030144829A1 (en) | 2002-01-25 | 2003-07-31 | Geatz Michael W. | System and method for sensing and evaluating physiological parameters and modeling an adaptable predictive analysis for symptoms management |
US6721603B2 (en) | 2002-01-25 | 2004-04-13 | Cyberonics, Inc. | Nerve stimulation as a treatment for pain |
US20030144711A1 (en) | 2002-01-29 | 2003-07-31 | Neuropace, Inc. | Systems and methods for interacting with an implantable medical device |
WO2003063949A2 (en) | 2002-02-01 | 2003-08-07 | The Cleveland Clinic Foundation | Adjustable simulation device and method of using same |
EP1478348A4 (en) | 2002-02-01 | 2008-06-18 | Cleveland Clinic Foundation | Microinfusion device |
WO2003066155A2 (en) | 2002-02-01 | 2003-08-14 | The Cleveland Clinic Foundation | Methods of affecting hypothalamic-related conditions |
AU2003210752A1 (en) | 2002-02-01 | 2003-09-02 | The Cleveland Clinic Foundation | Modulation of the pain circuitry to affect chronic pain |
WO2003072186A2 (en) | 2002-02-01 | 2003-09-04 | The Cleveland Clinic Foundation | Neurostimulation for affecting sleep disorders |
WO2003066124A2 (en) | 2002-02-01 | 2003-08-14 | The Cleveland Clinic Foundation | Apparatus for facilitating delivery of at least one device to a target site in a body |
US7493168B2 (en) | 2002-02-01 | 2009-02-17 | The Cleveland Clinic Foundation | Electrical stimulation to treat hair loss |
US7833174B2 (en) | 2002-02-01 | 2010-11-16 | The Cleveland Clinic Foundation | Method and apparatus for subcutaneously advancing a device between locations |
WO2003066153A2 (en) | 2002-02-01 | 2003-08-14 | The Cleveland Clinic Foundation | Neural stimulation delivery device with independently moveable delivery structures |
US6900421B2 (en) | 2002-02-08 | 2005-05-31 | Ecofriend Technologies, Inc. | Microwave-assisted steam sterilization of dental and surgical instruments |
US7043305B2 (en) | 2002-03-06 | 2006-05-09 | Cardiac Pacemakers, Inc. | Method and apparatus for establishing context among events and optimizing implanted medical device performance |
US8391989B2 (en) | 2002-12-18 | 2013-03-05 | Cardiac Pacemakers, Inc. | Advanced patient management for defining, identifying and using predetermined health-related events |
US7983759B2 (en) | 2002-12-18 | 2011-07-19 | Cardiac Pacemakers, Inc. | Advanced patient management for reporting multiple health-related parameters |
AUPS101502A0 (en) | 2002-03-11 | 2002-04-11 | Neopraxis Pty Ltd | Wireless fes system |
US7236822B2 (en) | 2002-03-22 | 2007-06-26 | Leptos Biomedical, Inc. | Wireless electric modulation of sympathetic nervous system |
US7239912B2 (en) | 2002-03-22 | 2007-07-03 | Leptos Biomedical, Inc. | Electric modulation of sympathetic nervous system |
US7689276B2 (en) | 2002-09-13 | 2010-03-30 | Leptos Biomedical, Inc. | Dynamic nerve stimulation for treatment of disorders |
US7221981B2 (en) | 2002-03-28 | 2007-05-22 | Northstar Neuroscience, Inc. | Electrode geometries for efficient neural stimulation |
EP1493097A1 (en) | 2002-04-05 | 2005-01-05 | Oliver Holzner | Method and device for the electromagnetic modification of cerebral activity |
JP4365558B2 (en) | 2002-04-08 | 2009-11-18 | 株式会社テクノ高槻 | Electromagnetic vibration type diaphragm pump |
EP1356762A1 (en) | 2002-04-22 | 2003-10-29 | UbiCom Gesellschaft für Telekommunikation mbH | Device for remote monitoring of body functions |
WO2003092796A1 (en) | 2002-05-03 | 2003-11-13 | Musc Foundation For Research Development | Method, apparatus and system for determining effects and optimizing parameters of vagus nerve stimulation |
US6825767B2 (en) | 2002-05-08 | 2004-11-30 | Charles Humbard | Subscription system for monitoring user well being |
US20060079936A1 (en) | 2003-05-11 | 2006-04-13 | Boveja Birinder R | Method and system for altering regional cerebral blood flow (rCBF) by providing complex and/or rectangular electrical pulses to vagus nerve(s), to provide therapy for depression and other medical disorders |
US7191012B2 (en) | 2003-05-11 | 2007-03-13 | Boveja Birinder R | Method and system for providing pulsed electrical stimulation to a craniel nerve of a patient to provide therapy for neurological and neuropsychiatric disorders |
US20050165458A1 (en) | 2002-05-09 | 2005-07-28 | Boveja Birinder R. | Method and system to provide therapy for depression using electroconvulsive therapy(ECT) and pulsed electrical stimulation to vagus nerve(s) |
US20060009815A1 (en) * | 2002-05-09 | 2006-01-12 | Boveja Birinder R | Method and system to provide therapy or alleviate symptoms of involuntary movement disorders by providing complex and/or rectangular electrical pulses to vagus nerve(s) |
US7885711B2 (en) * | 2003-06-13 | 2011-02-08 | Bio Control Medical (B.C.M.) Ltd. | Vagal stimulation for anti-embolic therapy |
US8036745B2 (en) * | 2004-06-10 | 2011-10-11 | Bio Control Medical (B.C.M.) Ltd. | Parasympathetic pacing therapy during and following a medical procedure, clinical trauma or pathology |
US7321793B2 (en) * | 2003-06-13 | 2008-01-22 | Biocontrol Medical Ltd. | Vagal stimulation for atrial fibrillation therapy |
US7292890B2 (en) | 2002-06-20 | 2007-11-06 | Advanced Bionics Corporation | Vagus nerve stimulation via unidirectional propagation of action potentials |
US20040015205A1 (en) | 2002-06-20 | 2004-01-22 | Whitehurst Todd K. | Implantable microstimulators with programmable multielectrode configuration and uses thereof |
US7006859B1 (en) * | 2002-07-20 | 2006-02-28 | Flint Hills Scientific, L.L.C. | Unitized electrode with three-dimensional multi-site, multi-modal capabilities for detection and control of brain state changes |
US6934580B1 (en) | 2002-07-20 | 2005-08-23 | Flint Hills Scientific, L.L.C. | Stimulation methodologies and apparatus for control of brain states |
US20040210270A1 (en) | 2002-07-26 | 2004-10-21 | John Erickson | High frequency pulse generator for an implantable neurostimulator |
US7020508B2 (en) | 2002-08-22 | 2006-03-28 | Bodymedia, Inc. | Apparatus for detecting human physiological and contextual information |
US8509897B2 (en) | 2002-09-19 | 2013-08-13 | Cardiac Pacemakers, Inc. | Morphology-based diagnostic monitoring of electrograms by implantable cardiac device |
US20050075679A1 (en) | 2002-09-30 | 2005-04-07 | Gliner Bradford E. | Methods and apparatuses for treating neurological disorders by electrically stimulating cells implanted in the nervous system |
US7209790B2 (en) | 2002-09-30 | 2007-04-24 | Medtronic, Inc. | Multi-mode programmer for medical device communication |
US7615010B1 (en) * | 2002-10-03 | 2009-11-10 | Integrated Sensing Systems, Inc. | System for monitoring the physiologic parameters of patients with congestive heart failure |
US8512252B2 (en) | 2002-10-07 | 2013-08-20 | Integrated Sensing Systems Inc. | Delivery method and system for monitoring cardiovascular pressures |
DE60335134D1 (en) | 2002-10-11 | 2011-01-05 | Flint Hills Scient Llc | MULTIMODAL SYSTEM FOR DETECTING AND CONTROLLING CHANGES IN THE STATE OF THE BRAIN |
US7204833B1 (en) | 2002-10-11 | 2007-04-17 | Flint Hills Scientific Llc | Multi-modal system for detection and control of changes in brain state |
EP1558130A4 (en) | 2002-10-15 | 2009-01-28 | Medtronic Inc | Screening techniques for management of a nervous system disorder |
WO2004036372A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Scoring of sensed neurological signals for use with a medical device system |
EP1558334B1 (en) | 2002-10-15 | 2015-03-18 | Medtronic, Inc. | Configuring and testing treatment therapy parameters for a medical device system |
US8738136B2 (en) * | 2002-10-15 | 2014-05-27 | Medtronic, Inc. | Clustering of recorded patient neurological activity to determine length of a neurological event |
WO2004034883A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Synchronization and calibration of clocks for a medical device and calibrated clock |
EP1558128B1 (en) | 2002-10-15 | 2014-04-30 | Medtronic, Inc. | Signal quality monitoring and control for a medical device system |
EP1629341A4 (en) | 2002-10-15 | 2008-10-15 | Medtronic Inc | Multi-modal operation of a medical device system |
AU2003285888A1 (en) | 2002-10-15 | 2004-05-04 | Medtronic Inc. | Medical device system with relaying module for treatment of nervous system disorders |
EP1558330A4 (en) | 2002-10-15 | 2008-10-01 | Medtronic Inc | Cycle mode providing redundant back-up to ensure termination of treatment therapy in a medical device system |
US7715919B2 (en) | 2002-10-15 | 2010-05-11 | Medtronic, Inc. | Control of treatment therapy during start-up and during operation of a medical device system |
WO2004036370A2 (en) | 2002-10-15 | 2004-04-29 | Medtronic Inc. | Channel-selective blanking for a medical device system |
US7236830B2 (en) | 2002-12-10 | 2007-06-26 | Northstar Neuroscience, Inc. | Systems and methods for enhancing or optimizing neural stimulation therapy for treating symptoms of Parkinson's disease and/or other movement disorders |
US7302298B2 (en) | 2002-11-27 | 2007-11-27 | Northstar Neuroscience, Inc | Methods and systems employing intracranial electrodes for neurostimulation and/or electroencephalography |
US20050075680A1 (en) | 2003-04-18 | 2005-04-07 | Lowry David Warren | Methods and systems for intracranial neurostimulation and/or sensing |
AU2003297761A1 (en) | 2002-12-09 | 2004-06-30 | Northstar Neuroscience, Inc. | Methods for treating neurological language disorders |
US6959215B2 (en) | 2002-12-09 | 2005-10-25 | Northstar Neuroscience, Inc. | Methods for treating essential tremor |
US20040111139A1 (en) | 2002-12-10 | 2004-06-10 | Mccreery Douglas B. | Apparatus and methods for differential stimulation of nerve fibers |
US7395117B2 (en) | 2002-12-23 | 2008-07-01 | Cardiac Pacemakers, Inc. | Implantable medical device having long-term wireless capabilities |
WO2004064918A1 (en) | 2003-01-14 | 2004-08-05 | Department Of Veterans Affairs, Office Of General Counsel | Cervical wagal stimulation induced weight loss |
KR100503519B1 (en) | 2003-01-22 | 2005-07-22 | 삼성전자주식회사 | Semiconductor device and Method of manufacturing the same |
US7085605B2 (en) | 2003-01-23 | 2006-08-01 | Epic Biosonics Inc. | Implantable medical assembly |
WO2004066825A2 (en) | 2003-01-31 | 2004-08-12 | The Board Of Trustees Of The Leland Stanford Junior University | Detection of apex motion for monitoring cardiac dysfunction |
US20050143781A1 (en) | 2003-01-31 | 2005-06-30 | Rafael Carbunaru | Methods and systems for patient adjustment of parameters for an implanted stimulator |
US7444183B2 (en) | 2003-02-03 | 2008-10-28 | Enteromedics, Inc. | Intraluminal electrode apparatus and method |
US20040172084A1 (en) | 2003-02-03 | 2004-09-02 | Knudson Mark B. | Method and apparatus for treatment of gastro-esophageal reflux disease (GERD) |
EP1603634B1 (en) | 2003-02-03 | 2011-12-21 | Enteromedics Inc. | Electrode band |
US7613515B2 (en) | 2003-02-03 | 2009-11-03 | Enteromedics Inc. | High frequency vagal blockage therapy |
US7844338B2 (en) * | 2003-02-03 | 2010-11-30 | Enteromedics Inc. | High frequency obesity treatment |
US7162307B2 (en) | 2003-02-11 | 2007-01-09 | Medtronic, Inc. | Channel occupancy in multi-channel medical device communication |
WO2004075982A1 (en) | 2003-02-21 | 2004-09-10 | Medtronic, Inc. | Implantable neurostimulator programming with battery longevity indication |
IL154801A0 (en) | 2003-03-06 | 2003-10-31 | Karotix Internat Ltd | Multi-channel and multi-dimensional system and method |
US20040199212A1 (en) | 2003-04-01 | 2004-10-07 | Fischell David R. | External patient alerting system for implantable devices |
US7377930B2 (en) | 2003-04-02 | 2008-05-27 | Frank Loughran | Nerve protecting tube |
US6901293B2 (en) | 2003-04-07 | 2005-05-31 | Medtronic, Inc. | System and method for monitoring power source longevity of an implantable medical device |
US20050004615A1 (en) | 2003-04-11 | 2005-01-06 | Sanders Richard S. | Reconfigurable implantable cardiac monitoring and therapy delivery device |
US20050187590A1 (en) | 2003-05-11 | 2005-08-25 | Boveja Birinder R. | Method and system for providing therapy for autism by providing electrical pulses to the vagus nerve(s) |
US7444184B2 (en) | 2003-05-11 | 2008-10-28 | Neuro And Cardial Technologies, Llc | Method and system for providing therapy for bulimia/eating disorders by providing electrical pulses to vagus nerve(s) |
US20060074450A1 (en) | 2003-05-11 | 2006-04-06 | Boveja Birinder R | System for providing electrical pulses to nerve and/or muscle using an implanted stimulator |
US7454251B2 (en) * | 2003-05-29 | 2008-11-18 | The Cleveland Clinic Foundation | Excess lead retaining and management devices and methods of using same |
CA2567051A1 (en) * | 2003-05-30 | 2004-12-23 | Michael Mathur | System, device, and method for remote monitoring and servicing |
US20040249302A1 (en) | 2003-06-09 | 2004-12-09 | Cyberkinetics, Inc. | Methods and systems for processing of brain signals |
US7149574B2 (en) * | 2003-06-09 | 2006-12-12 | Palo Alto Investors | Treatment of conditions through electrical modulation of the autonomic nervous system |
US7769465B2 (en) | 2003-06-11 | 2010-08-03 | Matos Jeffrey A | System for cardiac resuscitation |
US8214043B2 (en) | 2006-08-29 | 2012-07-03 | Matos Jeffrey A | Control of a defibrillator and/or pacemaker |
EP1648558A4 (en) * | 2003-06-13 | 2015-05-27 | Biocontrol Medical B C M Ltd | Applications of vagal stimulation |
AU2004249234B2 (en) | 2003-06-19 | 2009-03-12 | Advanced Neuromodulation Systems, Inc. | Method of treating depression, mood disorders and anxiety disorders using neuromodulation |
CA2432810A1 (en) | 2003-06-19 | 2004-12-19 | Andres M. Lozano | Method of treating depression, mood disorders and anxiety disorders by brian infusion |
WO2005007120A2 (en) | 2003-07-18 | 2005-01-27 | The Johns Hopkins University | System and method for treating nausea and vomiting by vagus nerve stimulation |
JP4960700B2 (en) | 2003-07-21 | 2012-06-27 | メタキュアー リミティド | Gastrointestinal treatment method and apparatus for use in treating disease and controlling blood glucose |
US6843870B1 (en) | 2003-07-22 | 2005-01-18 | Epic Biosonics Inc. | Implantable electrical cable and method of making |
US7249281B2 (en) * | 2003-07-28 | 2007-07-24 | Microsoft Corporation | Method and system for backing up and restoring data of a node in a distributed system |
US20050049515A1 (en) * | 2003-07-31 | 2005-03-03 | Dale Julian Misczynski | Electrode belt for acquisition, processing and transmission of cardiac (ECG) signals |
EP1654032A2 (en) * | 2003-08-01 | 2006-05-10 | Northstar Neuroscience, Inc. | Apparatus and methods for applying neural stimulation to a patient |
US7263405B2 (en) * | 2003-08-27 | 2007-08-28 | Neuro And Cardiac Technologies Llc | System and method for providing electrical pulses to the vagus nerve(s) to provide therapy for obesity, eating disorders, neurological and neuropsychiatric disorders with a stimulator, comprising bi-directional communication and network capabilities |
ITUD20030174A1 (en) | 2003-09-03 | 2005-03-04 | Sire Analytical Systems Srl | INTEGRATED SYSTEM FOR HEMATOLOGICAL ANALYSIS AND ITS METHOD. |
US7184837B2 (en) | 2003-09-15 | 2007-02-27 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using bayesian networks |
US7239926B2 (en) | 2003-09-15 | 2007-07-03 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using genetic algorithms |
US7617002B2 (en) * | 2003-09-15 | 2009-11-10 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using decision trees |
US7252090B2 (en) | 2003-09-15 | 2007-08-07 | Medtronic, Inc. | Selection of neurostimulator parameter configurations using neural network |
US7418292B2 (en) | 2003-10-01 | 2008-08-26 | Medtronic, Inc. | Device and method for attenuating an immune response |
US20050075702A1 (en) | 2003-10-01 | 2005-04-07 | Medtronic, Inc. | Device and method for inhibiting release of pro-inflammatory mediator |
US7561921B2 (en) | 2003-10-02 | 2009-07-14 | Medtronic, Inc. | Neurostimulator programmer with internal antenna |
US20050153885A1 (en) | 2003-10-08 | 2005-07-14 | Yun Anthony J. | Treatment of conditions through modulation of the autonomic nervous system |
US8467876B2 (en) * | 2003-10-15 | 2013-06-18 | Rmx, Llc | Breathing disorder detection and therapy delivery device and method |
US8190248B2 (en) * | 2003-10-16 | 2012-05-29 | Louisiana Tech University Foundation, Inc. | Medical devices for the detection, prevention and/or treatment of neurological disorders, and methods related thereto |
US6940255B2 (en) | 2003-10-23 | 2005-09-06 | Cardiac Pacemakers, Inc. | Battery charge indicator such as for an implantable medical device |
US20050131467A1 (en) | 2003-11-02 | 2005-06-16 | Boveja Birinder R. | Method and apparatus for electrical stimulation therapy for at least one of atrial fibrillation, congestive heart failure, inappropriate sinus tachycardia, and refractory hypertension |
US7248923B2 (en) | 2003-11-06 | 2007-07-24 | Cardiac Pacemakers, Inc. | Dual-use sensor for rate responsive pacing and heart sound monitoring |
US9002452B2 (en) | 2003-11-07 | 2015-04-07 | Cardiac Pacemakers, Inc. | Electrical therapy for diastolic dysfunction |
US20050113744A1 (en) | 2003-11-21 | 2005-05-26 | Cyberkinetics, Inc. | Agent delivery systems and related methods under control of biological electrical signals |
US7512438B2 (en) | 2003-11-26 | 2009-03-31 | Angel Medical Systems, Inc. | Implantable system for monitoring the condition of the heart |
WO2005053788A1 (en) | 2003-12-01 | 2005-06-16 | Medtronic, Inc. | Method and system for vagal nerve stimulation with multi-site cardiac pacing |
GB2408847B (en) | 2003-12-04 | 2006-11-01 | Agilent Technologies Inc | Semiconductor laser with integrated heating element and method of manufacturing same |
US20050124901A1 (en) | 2003-12-05 | 2005-06-09 | Misczynski Dale J. | Method and apparatus for electrophysiological and hemodynamic real-time assessment of cardiovascular fitness of a user |
US7783349B2 (en) | 2006-04-10 | 2010-08-24 | Cardiac Pacemakers, Inc. | System and method for closed-loop neural stimulation |
US7115096B2 (en) | 2003-12-24 | 2006-10-03 | Cardiac Pacemakers, Inc. | Third heart sound activity index for heart failure monitoring |
US7422555B2 (en) | 2003-12-30 | 2008-09-09 | Jacob Zabara | Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses |
US7254439B2 (en) | 2004-01-06 | 2007-08-07 | Monebo Technologies, Inc. | Method and system for contactless evaluation of fatigue of an operator |
US7164941B2 (en) | 2004-01-06 | 2007-01-16 | Dale Julian Misczynski | Method and system for contactless monitoring and evaluation of sleep states of a user |
US20050148895A1 (en) | 2004-01-06 | 2005-07-07 | Misczynski Dale J. | Method and apparatus for ECG derived sleep monitoring of a user |
US7107097B2 (en) | 2004-01-14 | 2006-09-12 | Northstar Neuroscience, Inc. | Articulated neural electrode assembly |
US7979137B2 (en) | 2004-02-11 | 2011-07-12 | Ethicon, Inc. | System and method for nerve stimulation |
US20050187593A1 (en) | 2004-02-23 | 2005-08-25 | Medtronic, Inc. | Implantable medical device system with communication link to home appliances |
DE102004014694A1 (en) | 2004-03-25 | 2005-10-27 | Universität Bremen | System and device in a tissue of living organisms implantable device for detecting and influencing electrical bio-activity |
US20050222631A1 (en) | 2004-04-06 | 2005-10-06 | Nirav Dalal | Hierarchical data storage and analysis system for implantable medical devices |
US20050228693A1 (en) | 2004-04-09 | 2005-10-13 | Webb James D | Data exchange web services for medical device systems |
CA2564122A1 (en) | 2004-04-28 | 2005-11-10 | Transoma Medical, Inc. | Implantable medical devices and related methods |
US20050245990A1 (en) | 2004-04-28 | 2005-11-03 | Joseph Roberson | Hearing implant with MEMS inertial sensor and method of use |
WO2005107854A2 (en) | 2004-05-04 | 2005-11-17 | The Cleveland Clinic Foundation | Corpus callosum neuromodulation assembly |
WO2005107859A1 (en) | 2004-05-04 | 2005-11-17 | The Cleveland Clinic Foundation | Methods of treating medical conditions by neuromodulation of the cerebellar pathways |
EP1804904A2 (en) | 2004-05-04 | 2007-07-11 | The Cleveland Clinic Foundation | Methods of treating neurological conditions by neuromodulation of interhemispheric fibers |
EP1595497A1 (en) | 2004-05-05 | 2005-11-16 | Drakeley Consulting Llc | Terminal device and wireless data transmission network |
US7697993B2 (en) | 2004-05-13 | 2010-04-13 | Cardiac Pacemakers, Inc. | Method and apparatus for question-based programming of cardiac rhythm management devices |
US7601115B2 (en) | 2004-05-24 | 2009-10-13 | Neuronetics, Inc. | Seizure therapy method and apparatus |
US20050277872A1 (en) | 2004-05-24 | 2005-12-15 | Colby John E Jr | Apparatus and method for mobile medical services |
WO2005117693A1 (en) | 2004-05-27 | 2005-12-15 | Children's Medical Center Corporation | Patient-specific seizure onset detection system |
US20050267550A1 (en) | 2004-05-28 | 2005-12-01 | Medtronic Minimed, Inc. | System and method for medical communication device and communication protocol for same |
US7801611B2 (en) | 2004-06-03 | 2010-09-21 | Cardiac Pacemakers, Inc. | System and method for providing communications between a physically secure programmer and an external device using a cellular network |
US7596413B2 (en) | 2004-06-08 | 2009-09-29 | Cardiac Pacemakers, Inc. | Coordinated therapy for disordered breathing including baroreflex modulation |
US7519430B2 (en) | 2004-06-17 | 2009-04-14 | Cardiac Pacemakers, Inc. | Dynamic telemetry encoding for an implantable medical device |
US7706866B2 (en) | 2004-06-24 | 2010-04-27 | Cardiac Pacemakers, Inc. | Automatic orientation determination for ECG measurements using multiple electrodes |
WO2006019822A2 (en) | 2004-07-14 | 2006-02-23 | Arizona Technology Enterprises | Pacemaker for treating physiological system dysfunction |
US7483747B2 (en) | 2004-07-15 | 2009-01-27 | Northstar Neuroscience, Inc. | Systems and methods for enhancing or affecting neural stimulation efficiency and/or efficacy |
EP1781372A1 (en) * | 2004-07-20 | 2007-05-09 | Medtronic, Inc. | Therapy programming guidance based on stored programming history |
US20060020491A1 (en) | 2004-07-20 | 2006-01-26 | Medtronic, Inc. | Batch processing method for patient management |
WO2006023636A1 (en) | 2004-08-18 | 2006-03-02 | Medtronic, Inc. | All-in-one interface for programmable implantable medical device |
US20050154425A1 (en) | 2004-08-19 | 2005-07-14 | Boveja Birinder R. | Method and system to provide therapy for neuropsychiatric disorders and cognitive impairments using gradient magnetic pulses to the brain and pulsed electrical stimulation to vagus nerve(s) |
DE102004043212A1 (en) | 2004-09-03 | 2006-03-09 | Biotronik Vi Patent Ag | Communication module and method for its operation |
JP4324059B2 (en) | 2004-09-03 | 2009-09-02 | 株式会社日立製作所 | IC tag mounting harness |
EP1804902A4 (en) | 2004-09-10 | 2008-04-16 | Cleveland Clinic Foundation | Intraluminal electrode assembly |
US20060058852A1 (en) * | 2004-09-10 | 2006-03-16 | Steve Koh | Multi-variable feedback control of stimulation for inspiratory facilitation |
CA2481631A1 (en) | 2004-09-15 | 2006-03-15 | Dspfactory Ltd. | Method and system for physiological signal processing |
US20060064133A1 (en) | 2004-09-17 | 2006-03-23 | Cardiac Pacemakers, Inc. | System and method for deriving relative physiologic measurements using an external computing device |
US20060064134A1 (en) | 2004-09-17 | 2006-03-23 | Cardiac Pacemakers, Inc. | Systems and methods for deriving relative physiologic measurements |
US7340302B1 (en) | 2004-09-27 | 2008-03-04 | Pacesetter, Inc. | Treating sleep apnea in patients using phrenic nerve stimulation |
US7890159B2 (en) | 2004-09-30 | 2011-02-15 | Cardiac Pacemakers, Inc. | Cardiac activation sequence monitoring and tracking |
US7509170B2 (en) | 2005-05-09 | 2009-03-24 | Cardiac Pacemakers, Inc. | Automatic capture verification using electrocardiograms sensed from multiple implanted electrodes |
US7167755B2 (en) | 2004-10-05 | 2007-01-23 | Cardiac Pacemakers, Inc. | Adaptive software configuration for a medical device |
US8175705B2 (en) | 2004-10-12 | 2012-05-08 | Cardiac Pacemakers, Inc. | System and method for sustained baroreflex stimulation |
US8755885B2 (en) | 2004-10-13 | 2014-06-17 | Medtronic, Inc. | Software configurable medical device platform and associated methods |
US7603174B2 (en) * | 2004-10-21 | 2009-10-13 | Advanced Neuromodulation Systems, Inc. | Stimulation of the amygdalohippocampal complex to treat neurological conditions |
WO2006047264A1 (en) * | 2004-10-21 | 2006-05-04 | Advanced Neuromodulation Systems, Inc. | Peripheral nerve stimulation to treat auditory dysfunction |
US8244355B2 (en) | 2004-10-29 | 2012-08-14 | Medtronic, Inc. | Method and apparatus to provide diagnostic index and therapy regulated by subject's autonomic nervous system |
US7672733B2 (en) * | 2004-10-29 | 2010-03-02 | Medtronic, Inc. | Methods and apparatus for sensing cardiac activity via neurological stimulation therapy system or medical electrical lead |
EP1827212B1 (en) | 2004-11-02 | 2010-09-22 | Medtronic, Inc. | Methods for data retention in an implantable medical device |
US7565200B2 (en) | 2004-11-12 | 2009-07-21 | Advanced Neuromodulation Systems, Inc. | Systems and methods for selecting stimulation sites and applying treatment, including treatment of symptoms of Parkinson's disease, other movement disorders, and/or drug side effects |
US20060106430A1 (en) | 2004-11-12 | 2006-05-18 | Brad Fowler | Electrode configurations for reducing invasiveness and/or enhancing neural stimulation efficacy, and associated methods |
WO2006053596A1 (en) | 2004-11-16 | 2006-05-26 | Cardiola Ltd. | Apparatus and method for the cardio-synchronized stimulation of skeletal or smooth muscles |
US20060122864A1 (en) | 2004-12-02 | 2006-06-08 | Gottesman Janell M | Patient management network |
US8374693B2 (en) | 2004-12-03 | 2013-02-12 | Cardiac Pacemakers, Inc. | Systems and methods for timing-based communication between implantable medical devices |
US7091231B2 (en) | 2004-12-10 | 2006-08-15 | Allergan, Inc. | 12-Aryl prostaglandin analogs |
US8112153B2 (en) | 2004-12-17 | 2012-02-07 | Medtronic, Inc. | System and method for monitoring or treating nervous system disorders |
US8108046B2 (en) | 2004-12-17 | 2012-01-31 | Medtronic, Inc. | System and method for using cardiac events to trigger therapy for treating nervous system disorders |
EP1833558B1 (en) * | 2004-12-17 | 2011-10-05 | Medtronic, Inc. | System for monitoring or treating nervous system disorders |
US8209009B2 (en) | 2004-12-17 | 2012-06-26 | Medtronic, Inc. | System and method for segmenting a cardiac signal based on brain stimulation |
US8112148B2 (en) | 2004-12-17 | 2012-02-07 | Medtronic, Inc. | System and method for monitoring cardiac signal activity in patients with nervous system disorders |
US8108038B2 (en) | 2004-12-17 | 2012-01-31 | Medtronic, Inc. | System and method for segmenting a cardiac signal based on brain activity |
US7547284B2 (en) * | 2005-01-14 | 2009-06-16 | Atlantis Limited Partnership | Bilateral differential pulse method for measuring brain activity |
DE102005003735B4 (en) | 2005-01-26 | 2008-04-03 | Cerbomed Gmbh | Device for transcutaneous stimulation of a nerve of the human body |
US8600521B2 (en) | 2005-01-27 | 2013-12-03 | Cyberonics, Inc. | Implantable medical device having multiple electrode/sensor capability and stimulation based on sensed intrinsic activity |
US7454245B2 (en) * | 2005-01-28 | 2008-11-18 | Cyberonics, Inc. | Trained and adaptive response in a neurostimulator |
US20060173493A1 (en) | 2005-01-28 | 2006-08-03 | Cyberonics, Inc. | Multi-phasic signal for stimulation by an implantable device |
WO2006083744A1 (en) | 2005-01-31 | 2006-08-10 | Medtronic, Inc. | Anchoring of a medical device component adjacent a dura of the brain or spinal cord |
CA2599959A1 (en) | 2005-03-01 | 2006-09-08 | Functional Neuroscience Inc. | Method of treating depression, mood disorders and anxiety disorders using neuromodulation |
US8700163B2 (en) | 2005-03-04 | 2014-04-15 | Cyberonics, Inc. | Cranial nerve stimulation for treatment of substance addiction |
US7889069B2 (en) | 2005-04-01 | 2011-02-15 | Codman & Shurtleff, Inc. | Wireless patient monitoring system |
US8473049B2 (en) * | 2005-05-25 | 2013-06-25 | Cardiac Pacemakers, Inc. | Implantable neural stimulator with mode switching |
US7542800B2 (en) | 2005-04-05 | 2009-06-02 | Cardiac Pacemakers, Inc. | Method and apparatus for synchronizing neural stimulation to cardiac cycles |
US20090048500A1 (en) | 2005-04-20 | 2009-02-19 | Respimetrix, Inc. | Method for using a non-invasive cardiac and respiratory monitoring system |
US20060241725A1 (en) | 2005-04-25 | 2006-10-26 | Imad Libbus | Method and apparatus for simultaneously presenting cardiac and neural signals |
US7640057B2 (en) | 2005-04-25 | 2009-12-29 | Cardiac Pacemakers, Inc. | Methods of providing neural markers for sensed autonomic nervous system activity |
US7310557B2 (en) | 2005-04-29 | 2007-12-18 | Maschino Steven E | Identification of electrodes for nerve stimulation in the treatment of eating disorders |
US7899540B2 (en) | 2005-04-29 | 2011-03-01 | Cyberonics, Inc. | Noninvasively adjustable gastric band |
US7835796B2 (en) | 2005-04-29 | 2010-11-16 | Cyberonics, Inc. | Weight loss method and device |
US7561923B2 (en) | 2005-05-09 | 2009-07-14 | Cardiac Pacemakers, Inc. | Method and apparatus for controlling autonomic balance using neural stimulation |
US8391990B2 (en) | 2005-05-18 | 2013-03-05 | Cardiac Pacemakers, Inc. | Modular antitachyarrhythmia therapy system |
US7551958B2 (en) | 2005-05-24 | 2009-06-23 | Cardiac Pacemakers, Inc. | Safety control system for implantable neural stimulator |
JP2006350707A (en) | 2005-06-16 | 2006-12-28 | Hitachi Ltd | Fault diagnosis device for detection means |
US20060293721A1 (en) | 2005-06-28 | 2006-12-28 | Cyberonics, Inc. | Vagus nerve stimulation for treatment of depression with therapeutically beneficial parameter settings |
EP1946794A1 (en) | 2005-07-20 | 2008-07-23 | Cyberonics, Inc. | Vagus nerve stimulation by electrical signals for controlling cerebellar tremor |
JP2009503285A (en) | 2005-07-22 | 2009-01-29 | クレケ,エドモンド | Temperature, heat and / or cold barrier |
US20070021786A1 (en) | 2005-07-25 | 2007-01-25 | Cyberonics, Inc. | Selective nerve stimulation for the treatment of angina pectoris |
WO2007018921A2 (en) | 2005-07-28 | 2007-02-15 | The General Hospital Corporation | Electro-optical system, aparatus, and method for ambulatory monitoring |
US7532935B2 (en) * | 2005-07-29 | 2009-05-12 | Cyberonics, Inc. | Selective neurostimulation for treating mood disorders |
US7790641B2 (en) | 2005-07-29 | 2010-09-07 | Fiberweb, Inc. | Bicomponent sheet material having liquid barrier properties |
US20070027486A1 (en) * | 2005-07-29 | 2007-02-01 | Cyberonics, Inc. | Medical devices for enhancing intrinsic neural activity |
US20070055320A1 (en) | 2005-09-07 | 2007-03-08 | Northstar Neuroscience, Inc. | Methods for treating temporal lobe epilepsy, associated neurological disorders, and other patient functions |
US20070073346A1 (en) | 2005-09-28 | 2007-03-29 | Giorgio Corbucci | Telemetry of combined endocavitary atrial and ventricular signals |
US8165682B2 (en) | 2005-09-29 | 2012-04-24 | Uchicago Argonne, Llc | Surface acoustic wave probe implant for predicting epileptic seizures |
US8010209B2 (en) | 2005-10-14 | 2011-08-30 | Nanostim, Inc. | Delivery system for implantable biostimulator |
US7729773B2 (en) | 2005-10-19 | 2010-06-01 | Advanced Neuromodualation Systems, Inc. | Neural stimulation and optical monitoring systems and methods |
US20070088403A1 (en) | 2005-10-19 | 2007-04-19 | Allen Wyler | Methods and systems for establishing parameters for neural stimulation |
US8929991B2 (en) | 2005-10-19 | 2015-01-06 | Advanced Neuromodulation Systems, Inc. | Methods for establishing parameters for neural stimulation, including via performance of working memory tasks, and associated kits |
US20070088404A1 (en) | 2005-10-19 | 2007-04-19 | Allen Wyler | Methods and systems for improving neural functioning, including cognitive functioning and neglect disorders |
US7856264B2 (en) | 2005-10-19 | 2010-12-21 | Advanced Neuromodulation Systems, Inc. | Systems and methods for patient interactive neural stimulation and/or chemical substance delivery |
US7620455B2 (en) | 2005-10-25 | 2009-11-17 | Cyberonics, Inc. | Cranial nerve stimulation to treat eating disorders |
US20070100377A1 (en) * | 2005-10-28 | 2007-05-03 | Cyberonics, Inc. | Providing multiple signal modes for a medical device |
US7832305B2 (en) | 2005-10-31 | 2010-11-16 | Dura Global Technologies Llc | Adjustable pedal system with low brake ratio change |
US8108048B2 (en) | 2005-11-30 | 2012-01-31 | Medtronic, Inc. | Protocol implementation for telemetry communications involving implantable medical devices |
US20090221882A1 (en) | 2005-12-08 | 2009-09-03 | Dan Gur Furman | Implantable Biosensor Assembly and Health Monitoring system and Method including same |
US20070135855A1 (en) | 2005-12-13 | 2007-06-14 | Foshee Phillip D | Patient management device for portably interfacing with a plurality of implantable medical devices and method thereof |
JP2009519803A (en) | 2005-12-20 | 2009-05-21 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | Device for detecting and notifying a medical condition |
US8046069B2 (en) | 2005-12-22 | 2011-10-25 | Cardiac Pacemakers, Inc. | Method and apparatus for control of cardiac therapy using non-invasive hemodynamic sensor |
US20070149952A1 (en) | 2005-12-28 | 2007-06-28 | Mike Bland | Systems and methods for characterizing a patient's propensity for a neurological event and for communicating with a pharmacological agent dispenser |
US9566447B2 (en) | 2005-12-28 | 2017-02-14 | Cardiac Pacemakers, Inc. | Neural stimulation system for reducing atrial proarrhythmia |
US8868172B2 (en) | 2005-12-28 | 2014-10-21 | Cyberonics, Inc. | Methods and systems for recommending an appropriate action to a patient for managing epilepsy and other neurological disorders |
US8725243B2 (en) | 2005-12-28 | 2014-05-13 | Cyberonics, Inc. | Methods and systems for recommending an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders |
US20070156450A1 (en) | 2006-01-04 | 2007-07-05 | Steven Roehm | Networked modular and remotely configurable system and method of remotely monitoring patient healthcare characteristics |
US8827905B2 (en) | 2006-01-04 | 2014-09-09 | General Electric Company | Patient initiated on-demand remote medical service with integrated knowledge base and computer assisted diagnosing characteristics |
US20080051852A1 (en) * | 2006-01-21 | 2008-02-28 | Cerbomed Gmbh | Device and method for the transdermal stimulation of a nerve of the human body |
US7606622B2 (en) | 2006-01-24 | 2009-10-20 | Cardiac Pacemakers, Inc. | Method and device for detecting and treating depression |
US7974697B2 (en) * | 2006-01-26 | 2011-07-05 | Cyberonics, Inc. | Medical imaging feedback for an implantable medical device |
US7801601B2 (en) * | 2006-01-27 | 2010-09-21 | Cyberonics, Inc. | Controlling neuromodulation using stimulus modalities |
US20070179558A1 (en) | 2006-01-30 | 2007-08-02 | Gliner Bradford E | Systems and methods for varying electromagnetic and adjunctive neural therapies |
US20070287931A1 (en) | 2006-02-14 | 2007-12-13 | Dilorenzo Daniel J | Methods and systems for administering an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders |
US20070208390A1 (en) | 2006-03-01 | 2007-09-06 | Von Arx Jeffrey A | Implantable wireless sound sensor |
US8209018B2 (en) | 2006-03-10 | 2012-06-26 | Medtronic, Inc. | Probabilistic neurological disorder treatment |
ES2566730T3 (en) | 2006-03-29 | 2016-04-15 | Dignity Health | Synchronization of vagus nerve stimulation with a patient's cardiac cycle |
US7496409B2 (en) | 2006-03-29 | 2009-02-24 | Medtronic, Inc. | Implantable medical device system and method with signal quality monitoring and response |
AU2012202405B2 (en) | 2006-03-29 | 2013-11-21 | Catholic Healthcare West | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
AU2012202408B2 (en) | 2006-03-29 | 2014-01-16 | Catholic Healthcare West | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US20070239211A1 (en) | 2006-03-31 | 2007-10-11 | Andras Lorincz | Embedded neural prosthesis |
US8926676B2 (en) | 2006-04-11 | 2015-01-06 | Advanced Neuromodulation Systems, Inc. | Systems and methods for applying signals, including contralesional signals, to neural populations |
US7949401B2 (en) * | 2006-04-11 | 2011-05-24 | Advanced Neuromodulation Systems, Inc. | Electromagnetic signal delivery for tissue affected by neuronal dysfunction, degradation, damage, and/or necrosis, and associated systems and methods |
US20070249953A1 (en) | 2006-04-21 | 2007-10-25 | Medtronic, Inc. | Method and apparatus for detection of nervous system disorders |
US8165683B2 (en) | 2006-04-21 | 2012-04-24 | Medtronic, Inc. | Method and apparatus for detection of nervous system disorders |
US20070249956A1 (en) | 2006-04-21 | 2007-10-25 | Medtronic, Inc. | Method and apparatus for detection of nervous system disorders |
US7761145B2 (en) | 2006-04-21 | 2010-07-20 | Medtronic, Inc. | Method and apparatus for detection of nervous system disorders |
US8155742B2 (en) | 2006-04-25 | 2012-04-10 | Medtronic, Inc. | Remote communication system with availability indicator for an implantable medical device |
US7912537B2 (en) | 2006-04-27 | 2011-03-22 | Medtronic, Inc. | Telemetry-synchronized physiological monitoring and therapy delivery systems |
US7764988B2 (en) | 2006-04-27 | 2010-07-27 | Medtronic, Inc. | Flexible memory management scheme for loop recording in an implantable device |
US7610083B2 (en) | 2006-04-27 | 2009-10-27 | Medtronic, Inc. | Method and system for loop recording with overlapping events |
US7962220B2 (en) | 2006-04-28 | 2011-06-14 | Cyberonics, Inc. | Compensation reduction in tissue stimulation therapy |
US20070255337A1 (en) | 2006-04-28 | 2007-11-01 | Medtronic, Inc. | Cardiac monitoring via gastrointestinal stimulator |
US7856272B2 (en) | 2006-04-28 | 2010-12-21 | Flint Hills Scientific, L.L.C. | Implantable interface for a medical device system |
NL1031958C2 (en) | 2006-06-07 | 2007-12-10 | Hobo Heeze B V | Personal monitoring system for real-time signaling of epilepsy attacks. |
US7676263B2 (en) * | 2006-06-23 | 2010-03-09 | Neurovista Corporation | Minimally invasive system for selecting patient-specific therapy parameters |
US20080046038A1 (en) * | 2006-06-26 | 2008-02-21 | Hill Gerard J | Local communications network for distributed sensing and therapy in biomedical applications |
US7949404B2 (en) | 2006-06-26 | 2011-05-24 | Medtronic, Inc. | Communications network for distributed sensing and therapy in biomedical applications |
US8170668B2 (en) * | 2006-07-14 | 2012-05-01 | Cardiac Pacemakers, Inc. | Baroreflex sensitivity monitoring and trending for tachyarrhythmia detection and therapy |
DE102006036069B4 (en) * | 2006-07-18 | 2008-09-04 | Cerbomed Gmbh | Audiological transmission system |
DE102006033623B4 (en) | 2006-07-18 | 2010-04-08 | Cerbomed Gmbh | System for transcutaneous stimulation of a nerve of the human body |
AU2007281122A1 (en) | 2006-08-02 | 2008-02-07 | Advanced Neuromodulation Systems, Inc. | Methods for treating neurological disorders, including neuropsychiatric and neuropsychological disorders, and associated systems |
US20080046037A1 (en) * | 2006-08-18 | 2008-02-21 | Haubrich Gregory J | Wireless Communication Network for an Implantable Medical Device System |
US8121692B2 (en) * | 2006-08-30 | 2012-02-21 | Cardiac Pacemakers, Inc. | Method and apparatus for neural stimulation with respiratory feedback |
AU2007294526B2 (en) | 2006-09-08 | 2011-07-07 | Cardiomems, Inc. | Physiological data acquisition and management system for use with an implanted wireless sensor |
US8126529B2 (en) | 2006-09-22 | 2012-02-28 | Advanced Neuromodulation Systems, Inc. | Methods and systems for securing electrode leads |
US20080077028A1 (en) | 2006-09-27 | 2008-03-27 | Biotronic Crm Patent | Personal health monitoring and care system |
US8123668B2 (en) | 2006-09-28 | 2012-02-28 | Bioventrix (A Chf Technologies' Company) | Signal transmitting and lesion excluding heart implants for pacing defibrillating and/or sensing of heart beat |
WO2008052082A2 (en) | 2006-10-24 | 2008-05-02 | Northstar Neuroscience, Inc. | Frequency shift keying (fsk) magnetic telemetry system for implantable medical devices and associated systems and methods |
US8295934B2 (en) | 2006-11-14 | 2012-10-23 | Neurovista Corporation | Systems and methods of reducing artifact in neurological stimulation systems |
US8096954B2 (en) | 2006-11-29 | 2012-01-17 | Cardiac Pacemakers, Inc. | Adaptive sampling of heart sounds |
US20080139870A1 (en) | 2006-12-12 | 2008-06-12 | Northstar Neuroscience, Inc. | Systems and methods for treating patient hypertonicity |
US8652040B2 (en) | 2006-12-19 | 2014-02-18 | Valencell, Inc. | Telemetric apparatus for health and environmental monitoring |
US20080161712A1 (en) | 2006-12-27 | 2008-07-03 | Kent Leyde | Low Power Device With Contingent Scheduling |
US9913593B2 (en) | 2006-12-27 | 2018-03-13 | Cyberonics, Inc. | Low power device with variable scheduling |
US20080183097A1 (en) | 2007-01-25 | 2008-07-31 | Leyde Kent W | Methods and Systems for Measuring a Subject's Susceptibility to a Seizure |
WO2008092119A2 (en) | 2007-01-25 | 2008-07-31 | Neurovista Corporation | Systems and methods for identifying a contra-ictal condition in a subject |
US20080183245A1 (en) | 2007-01-31 | 2008-07-31 | Van Oort Geeske | Telemetry of external physiological sensor data and implantable medical device data to a central processing system |
US7747551B2 (en) | 2007-02-21 | 2010-06-29 | Neurovista Corporation | Reduction of classification error rates and monitoring system using an artificial class |
US20080208074A1 (en) | 2007-02-21 | 2008-08-28 | David Snyder | Methods and Systems for Characterizing and Generating a Patient-Specific Seizure Advisory System |
US8068918B2 (en) | 2007-03-09 | 2011-11-29 | Enteromedics Inc. | Remote monitoring and control of implantable devices |
US8036736B2 (en) | 2007-03-21 | 2011-10-11 | Neuro Vista Corporation | Implantable systems and methods for identifying a contra-ictal condition in a subject |
US20080249591A1 (en) | 2007-04-06 | 2008-10-09 | Northstar Neuroscience, Inc. | Controllers for implantable medical devices, and associated methods |
US20080255582A1 (en) | 2007-04-11 | 2008-10-16 | Harris John F | Methods and Template Assembly for Implanting an Electrode Array in a Patient |
US20090054795A1 (en) | 2007-08-22 | 2009-02-26 | Misczynski Dale J | Method for generating three standard surface ecg leads derived from three electrodes contained in the mid-horizontal plane of the torso |
US7643293B2 (en) | 2007-12-18 | 2010-01-05 | Hon Hai Precision Industry Co., Ltd. | Heat dissipation device and a method for manufacturing the same |
US8080196B2 (en) | 2008-02-12 | 2011-12-20 | Gala Industries, Inc. | Method and apparatus to achieve crystallization of polymers utilizing multiple processing systems |
-
2007
- 2007-03-29 ES ES07759722.7T patent/ES2566730T3/en active Active
- 2007-03-29 EP EP15168839.7A patent/EP2965781B1/en active Active
- 2007-03-29 CA CA2653110A patent/CA2653110C/en not_active Expired - Fee Related
- 2007-03-29 AU AU2007233135A patent/AU2007233135B2/en not_active Ceased
- 2007-03-29 EP EP18161805.9A patent/EP3363495A1/en not_active Withdrawn
- 2007-03-29 BR BRPI0709844-8A patent/BRPI0709844A2/en not_active Application Discontinuation
- 2007-03-29 EP EP20070759728 patent/EP2026874B1/en not_active Not-in-force
- 2007-03-29 ES ES07759728.4T patent/ES2538726T3/en active Active
- 2007-03-29 EP EP15161760.2A patent/EP2918310B1/en not_active Not-in-force
- 2007-03-29 CA CA2653112A patent/CA2653112C/en not_active Expired - Fee Related
- 2007-03-29 ES ES07759710.2T patent/ES2573323T3/en active Active
- 2007-03-29 WO PCT/US2007/065518 patent/WO2007115103A1/en active Application Filing
- 2007-03-29 EP EP07759710.2A patent/EP2007477B1/en not_active Not-in-force
- 2007-03-29 EP EP16164873.8A patent/EP3069752B1/en not_active Not-in-force
- 2007-03-29 AU AU2007233205A patent/AU2007233205B2/en not_active Ceased
- 2007-03-29 WO PCT/US2007/065537 patent/WO2007115118A1/en active Application Filing
- 2007-03-29 WO PCT/US2007/065531 patent/WO2007115113A1/en active Application Filing
- 2007-03-29 CA CA3006219A patent/CA3006219A1/en not_active Abandoned
- 2007-03-29 JP JP2009503285A patent/JP5052596B2/en active Active
- 2007-03-29 US US11/693,421 patent/US8150508B2/en active Active
- 2007-03-29 US US11/693,499 patent/US8219188B2/en active Active
- 2007-03-29 BR BRPI0709850-2A patent/BRPI0709850A2/en not_active IP Right Cessation
- 2007-03-29 US US11/693,451 patent/US8615309B2/en active Active
- 2007-03-29 EP EP07759722.7A patent/EP2004283B1/en not_active Not-in-force
- 2007-03-29 JP JP2009503279A patent/JP5415255B2/en active Active
-
2008
- 2008-09-28 IL IL194407A patent/IL194407A/en not_active IP Right Cessation
- 2008-09-28 IL IL194406A patent/IL194406A/en not_active IP Right Cessation
-
2009
- 2009-03-10 US US12/401,026 patent/US8738126B2/en active Active
- 2009-03-10 US US12/400,893 patent/US8280505B2/en active Active
- 2009-03-10 US US12/400,970 patent/US8660666B2/en active Active
-
2012
- 2012-04-03 US US13/438,645 patent/US9289599B2/en active Active
- 2012-11-02 JP JP2012242653A patent/JP2013031708A/en not_active Withdrawn
-
2013
- 2013-11-25 US US14/089,185 patent/US9108041B2/en active Active
-
2014
- 2014-01-10 US US14/152,428 patent/US9533151B2/en active Active
- 2014-04-09 US US14/248,893 patent/US10835749B2/en active Active
-
2015
- 2015-08-20 US US14/830,828 patent/US20150352362A1/en active Pending
-
2016
- 2016-02-16 US US15/044,320 patent/US11116978B2/en active Active
-
2020
- 2020-06-13 US US16/900,878 patent/US20200306541A1/en active Pending
- 2020-11-06 US US17/091,177 patent/US11771902B2/en active Active
-
2023
- 2023-09-22 US US18/371,882 patent/US20240009462A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993021824A1 (en) * | 1992-04-24 | 1993-11-11 | Medtronic, Inc. | Implantable electrical vagal stimulation for prevention or interruption of life threatening arrhythmias |
US20040138721A1 (en) * | 1999-04-30 | 2004-07-15 | Medtronic, Inc. | Vagal nerve stimulation techniques for treatment of epileptic seizures |
US20050267542A1 (en) * | 2001-08-31 | 2005-12-01 | Biocontrol Medical Ltd. | Techniques for applying, configuring, and coordinating nerve fiber stimulation |
EP1486232A2 (en) * | 2002-06-12 | 2004-12-15 | Pacesetter, Inc. | Device for improving cardiac funtion in heart failure or CHF patients |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9108041B2 (en) | 2006-03-29 | 2015-08-18 | Dignity Health | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
US9289599B2 (en) | 2006-03-29 | 2016-03-22 | Dignity Health | Vagus nerve stimulation method |
US9533151B2 (en) | 2006-03-29 | 2017-01-03 | Dignity Health | Microburst electrical stimulation of cranial nerves for the treatment of medical conditions |
WO2010047760A1 (en) * | 2008-10-20 | 2010-04-29 | Cyberonics, Inc. | Neurostimulation with signal duration determined by a cardiac cycle |
US8457747B2 (en) | 2008-10-20 | 2013-06-04 | Cyberonics, Inc. | Neurostimulation with signal duration determined by a cardiac cycle |
US8874218B2 (en) | 2008-10-20 | 2014-10-28 | Cyberonics, Inc. | Neurostimulation with signal duration determined by a cardiac cycle |
CN108126274A (en) * | 2014-12-21 | 2018-06-08 | 徐志强 | The multi-channel nerve stimulating apparatus of impulse stimulation is carried out to depth stupor brain |
CN108126274B (en) * | 2014-12-21 | 2022-04-08 | 徐志强 | Multichannel nerve stimulation device for pulse stimulation of deep coma brain |
EP3793671A4 (en) * | 2018-05-15 | 2022-02-23 | Livanova USA, Inc. | Display signal to asses autonomic response to vagus nerve stimulation treatment |
EP3793668A4 (en) * | 2018-05-15 | 2022-03-02 | Livanova USA, Inc. | Poincare display to assess autonomic engagement responsive to vagus nerve stimulation |
EP3793669A4 (en) * | 2018-05-15 | 2022-03-02 | Livanova USA, Inc. | R-r interval analysis for ecg waveforms to assess autonomic response to vagus nerve simulation |
US11752341B2 (en) | 2018-05-15 | 2023-09-12 | Livanova Usa, Inc. | Display signal to assess autonomic response to vagus nerve stimulation treatment |
US11786740B2 (en) | 2018-05-15 | 2023-10-17 | Livanova Usa, Inc. | Assessment system with wand detection cable synchronizing ECG recording |
US11786732B2 (en) | 2018-05-15 | 2023-10-17 | Livanova Usa, Inc. | R-R interval analysis for ECG waveforms to assess autonomic response to vagus nerve stimulation |
US11794015B2 (en) | 2018-05-15 | 2023-10-24 | Livanova Us, Inc. | Poincare display to assess autonomic engagement responsive to vagus nerve stimulation |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20200306541A1 (en) | Vagus nerve stimulation method | |
US10653883B2 (en) | Implantable medical device for providing chronic condition therapy and acute condition therapy using vagus nerve stimulation | |
AU2018300009B2 (en) | Systems and methods for respiratory-gated nerve stimulation | |
AU2012202405A1 (en) | Synchronization of vagus nerve stimulation with the cardiac cycle of a patient |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 07759728 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007759728 Country of ref document: EP |